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A sample of 147 men drawn from the workers in a pulp mill was compared with one of 124 men from a paper mill. The former included those exposed to chlorine and to sulphur dioxide. No significant differences were found in respiratory symptoms or in simple tests of ventilatory function in the two samples, but men working in chlorine had a somewhat poorer respiratory function and more shortness of breath than those working in sulphur dioxide. The working population of both mills together had a lower prevalence of respiratory disease than that of the male population of Berlin, N.H., previously studied, suggesting that working populations may not be representative of the general population. Further, a low prevalence of disease in a working population exposed to pollutants may not indicate their `safety9 in general populations.

Background Despite efforts to reduce exposure to secondhand smoke (SHS), only 5% of the world9s population enjoy smoke-free restaurants and bars. Methods Lifetime excess risk (LER) of cancer death, ischaemic heart disease (IHD) death and asthma initiation among non-smoking restaurant and bar servers and patrons in Minnesota and the US were estimated using weighted field measurements of SHS constituents in Minnesota, existing data on tobacco use and multiple dose-response models. Results A continuous approach estimated a LER of lung cancer death (LCD) of 18×10 −6 (95% CI 13 to 23×10 −6 ) for patrons visiting only designated non-smoking sections, 80×10 −6 (95% CI 66 to 95×10 −6 ) for patrons visiting only smoking venues/sections and 802×10 −6 (95% CI 658 to 936×10 −6 ) for servers in smoking-permitted venues. An attributable-risk (exposed/non-exposed) approach estimated a similar LER of LCD, a LER of IHD death about 10 −2 for non-smokers with average SHS exposure from all sources and a LER of asthma initiation about 5% for servers with SHS exposure at work only. These risks correspond to 214 LCDs and 3001 IHD deaths among the general non-smoking population and 1420 new asthma cases among non-smoking servers in the US each year due to SHS exposure in restaurants and bars alone. Conclusions Health risks for patrons and servers from SHS exposure in restaurants and bars alone are well above the acceptable level. Restaurants and bars should be a priority for governments’ effort to create smoke-free environments and should not be exempt from smoking bans.

Objectives The objective of this study was to evaluate the impact of 100% smoke-free environment legislation on respiratory and sensory irritation symptoms and respiratory function among bar and restaurant workers from the city of Neuquén, Argentina. Methods Pre-ban and post-ban studies without a comparison group in an Argentinean city were conducted. A baseline survey and spirometric measurements were performed with a total of 80 bar and restaurant workers 1 month before (October 2007) and 3 months after (March 2008) the implementation of the new 100% smoke-free legislation. Results A significant reduction in secondhand smoke exposure was observed after the enactment and enforcement of the new legislation, and an important reduction in respiratory symptoms (from a pre-ban level of 57.5% to a post-ban level of only 28.8%). The reduction of sensory irritation symptoms was even higher. From 86.3% of workers who reported at least one sensory irritation symptom in October 2007, only 37.5% reported the same symptoms in March 2008. Also, data obtained by spirometry showed a significant forced vital capacity increase. Conclusions Consistent with other studies, 100% smoke-free legislation improved short-term health outcomes in the sample and should be implemented nationwide. Furthermore, undertaking this study has been highly important in promoting 100% smoke-free environment legislation at the workplace as a legitimate right of hospitality workers, and in reducing social acceptance of designated smoking areas in bars and restaurants.

OBJECTIVES—Some patients with occupational asthma resulting from exposure to reactive dyes have skin reactivity to the causative dyes and specific IgE to reactive dyes have been found in these patients. However, the usefulness of skin prick tests (SPTs) and serological measurement of specific IgE in screening, diagnosis, and monitoring the occupational asthma resulting from exposure to reactive dyes have not yet been assessed. In this study, the clinical validation of SPTs and measurement of specific IgE to vinyl sulphone reactive dyes by enzyme linked immunosorbent assay (ELISA) was evaluated. METHODS— 42 Patients with occupational asthma from reactive dyes (true positive group) were enrolled. In these the causative reactive dye was confirmed by bronchial challenge test. 93 Asymptomatic factory workers with negative challenge to the reactive dye (true negative group) and 16 unexposed controls with negative challenge to the reactive dye were also enrolled. Skin prick tests were done with 10 mg/ml reactive dye in 0.4% phenol/0.9% saline. IgE specific to reactive dye conjugated to human serum albumin (HSA) was measured with enzyme linked immunosorbent assays (ELISAs). RESULTS—None of the unexposed controls had a positive response to SPTs. The sensitivity (76.2% v 53.7%), specificity (91.4% v 86.0%), positive predictive value (80.0% v 62.9%), and negative predictive value (89.5% v 80.8%) of SPTs were higher than those of ELISAs. The mean weal size of reaction to reactive dye was weakly correlated with the ELISA optical density of IgE to reactive dye conjugate in patients with occupational asthma from reactive dyes (n=41, r=0.337, p

OBJECTIVES—To analyze factors that determine the occurrence of sickness absence due to respiratory disorders and the time it takes to return to work. METHODS—A longitudinal study with 2 year follow up was conducted among 326 male blue collar and white collar workers. The survey started with an interview on respiratory complaints and spirometry. Sixty six (21%) workers were lost to follow up. Complete data on sickness absence among 251 workers during the follow up were collected from absence records and self reports. Regression analysis based on a proportional hazards model was applied to identify risk factors for the occurrence and duration of sickness absence due to respiratory disorders. RESULTS—During the follow up 35% workers attributed at least one period of sickness absence to respiratory complaints, which accounted for 14.2% of all days lost. A history of chronic obstructive pulmonary disease (COPD) did not predict sickness absence for COPD; the same was true for chronic non-specific lung disease (CNSLD). Complaints about asthma contributed significantly to absence due to asthma (relative risk (RR) 3.96; 95% confidence interval (95% CI) 1.99 to 7.90). Job title was a significant predictor of sickness absence due to respiratory complaints. Decrease in forced vital capacity (FVC

OBJECTIVES—To examine trends in estimated population based incidence of occupational asthma by age, sex, occupation, geographical region, and causal agents based on 9 years of the Surveillance of Work Related and Occupational Respiratory Disease (SWORD) data. METHODS—In January 1989 the SWORD scheme for the surveillance of occupational respiratory disease was established in the United Kingdom to make good the lack of epidemiological information on the incidence of these diseases in the United Kingdom. Between 80% and 90% of chest and occupational physicians report voluntarily all new cases they see, on a monthly or random sampling basis. During the 9 years 1989-97, an estimated 25 674 new cases of occupational respiratory disease, including 7387 of occupational asthma, were reported. Suspected causal agents were classified into 44 categories and estimated annual incidences of asthma were calculated with denominators from the labour force survey. RESULTS—Overall, a third of the suspected causes of asthma were organic, a third chemical, 6% metallic, and the rest miscellaneous, or in 8%, unknown. There was evidence of an increase since 1989 in cases due to latex, and possibly glutaraldehyde, and an apparent drop since 1991 in the proportion of cases attributed to isocyanates. Incidences were higher in men than women and the disparity was especially marked in the population aged 45 years or more in which rates for men were at least twice those for women. Average annual rates per million workers for 1992-7 ranged from 7 (95% confidence interval (95% CI) 5 to 9) for the lowest risk group of professional, clerical, and service workers to 1464 (95% CI 968 to 2173) for coach and other spray painters. Except for laboratory technicians, all other occupations with rates over 100 were concerned with manufacturing and processing that used chemicals, metals, and organic materials. Incidences were two to three times higher in the north and midlands than in East Anglia and the south. The introduction of a sampling scheme in 1992 doubled estimates of reported incidence of occupational asthma, but there was little evidence of other temporal changes. CONCLUSIONS—The SWORD scheme has produced consistent estimates of the causes and incidence of occupational asthma as seen by chest and occupational physicians. It has allowed the epidemiology of occupational asthma in the population to be studied and high risk occupations to be identified. There is certainly more occupational asthma in the population than that which reaches specialists in occupational and chest medicine; therefore the incidence rates presented here are underestimates, but by how much remains unknown. Keywords: occupational asthma; incidence; regional differences

OBJECTIVES—The importance of airborne fungal and other spores in provoking asthma attacks is uncertain. Panel studies have generated evidence that suggests a link between outdoor spore counts and severity of asthma. There have been no population based time series studies relating outdoor exposure to spores with incidence of attacks of asthma. METHODS—Outcomes were hospital admissions for asthma on 2002 days during 1987-94, for children and adults in the Trent region of England. Predictors were daily counts of 25 spore taxa from volumetric traps in Derby on the same and previous day. Admissions for asthma were adjusted for weekly, seasonal, and longer term trends by log linear autoregressive models. Spore counts on 6 days of asthma epidemics were also examined. RESULTS—When spore counts for individual taxa were analysed as quantitative variables, two positive and two negative correlations (out of a possible 100) were significant at the 5% level. When spore counts were dichotomised at the 90th percentile, one negative and eight positive correlations (out of 100) were significant at the 5% level. All significantly positive associations related to admissions among children, but none involved the total spore count. However, total spores were above the 90th percentile on four of the six epidemic days (odds ratio (OR) 9.92, 95% confidence interval (95% CI) 1.41 to 109.84), but epidemics occurred on only four of 343 days with high total moulds. CONCLUSIONS—There was some evidence that exceptional rates of admission for asthma tend to occur on days with high total mould spore counts, but no specific taxon was consistently implicated. The predictive power was insufficient to support a public warning system. Keywords: asthma; hospital admissions; moulds; fungi; spore counts; aeroallergens; log linear autoregression

OBJECTIVES—To investigate the short term effects of air pollution on the respiratory morbidity of children living in Sao Paulo, Brazil, one of the largest cities in the developing world. METHODS—Daily counts of hospital admissions due to respiratory diseases along with daily levels of meteorological variables and air pollutants (PM10, SO2, NO2, O3, and CO) were analysed with Poisson regression. Final models were adjusted for the effects of time trends, seasonal patterns, weekdays, holidays, meteorological factors, and serial correlation. RESULTS—Daily admissions of children to hospital for total respiratory disease and pneumonia showed significant increases associated with O3 (5-8%), NO2 (9%), and with PM10 (9%) (results are for an increase from the 10th to the 90th percentile of pollution measurements). Consistently, effects for pneumonia were greater than for all respiratory diseases combined. Also, effects on infants (children

To examine the benefits of adding salmeterol compared with increasing dose of inhaled corticosteroids.Systematic review of randomised, double blind clinical trials. Independent data extraction and validation with summary data from study reports and manuscripts. Fixed and random effects analyses.EMBASE, Medline, and GlaxoWellcome internal clinical study registers.Efficacy and exacerbations.Among 2055 trials of treatment with salmeterol, there were nine parallel group trials of/=12 weeks with 3685 symptomatic patients aged/=12 years taking inhaled steroid in primary or secondary care. Compared with response to increased steroids, in patients receiving salmeterol morning peak expiratory flow was greater at three months (difference 22.4 (95% confidence interval 15.0 to 30.0) litre/min, P0.001) and six months (27.7 (19.0 to 36.4) litre/min, P0.001). Forced expiratory volume in one second (FEV(1)) was also increased at three months (0.10 (0.04 to 0.16) litres, P0.001) and six months (0.08 (0.02 to 0.14) litres, P0.01), as were mean percentage of days and nights without symptoms (three months: days-12% (9% to 15%), nights-5% (3% to 7%); six months: days-15% (12% to 18%), nights-5% (3% to 7%); all P0.001) and mean percentage of days and nights without need for rescue treatment (three months: days-17% (14% to 20%), nights-9% (7% to 11%); six months: days-20% (17 to 23%), nights-8% (6% to 11%); all P0.001). Fewer patients experienced any exacerbation with salmeterol (difference 2.73% (0.43% to 5.04%), P=0. 02), and the proportion of patients with moderate or severe exacerbations was also lower (2.42% (0.24% to 4.60%), P=0.03).Addition of salmeterol in symptomatic patients aged 12 and over on low to moderate doses of inhaled steroid gives improved lung function and increased number of days and nights without symptoms or need for rescue treatment with no increase in exacerbations of any severity.

OBJECTIVES—To explore relations between two estimates of exposure to inhalable flour dust, and the incidence rates (IRs) of asthma and rhinitis in bakers. METHODS—This was a retrospective cohort study among 2923 bakers. A posted questionnaire registered the disease and work history. For every year, each baker was assigned an estimate of the exposure concentration to inhalable flour dust derived from reported job-tasks and dust measurements. Exposure at onset of disease was expressed as current dust exposure concentration, and as cumulative dose of exposure to dust. A multiple Poisson regression analysis assessed the impacts of the exposure estimates on the IRs of asthma and rhinitis. RESULTS—IRs of asthma and rhinitis increased by dust concentration at onset of disease. The IR of asthma for the bakers with highest exposure (dough makers) was 7.3/1000 person-years in men and 6.5 in women and for rhinitis 43.4 and 38.5, respectively. There was a significant association between the dust concentration at onset of disease and the risk for asthma or rhinitis, but not of the cumulative exposure. CONCLUSION—The risk of asthma seemed to be increased at inhalable dust concentrations ⩾3 mg/m3 (dough making or bread forming), whereas the risk of rhinitis was increased at all concentrations ⩾1 mg/m3, indicating an increased risk in all bakery job-tasks. The risks seemed to be less dependent on the cumulative exposure dust than the inhalable dust concentrations. Keywords: bakers; exposure-response relations; flour dust

To investigate the influence of weight reduction on obese patients with asthma.Open study, two randomised parallel groups.Private outpatients centre, Helsinki, Finland.Two groups of 19 obese patients with asthma (body mass index (kg/m(2)) 30 to 42) recruited through newspaper advertisements.Supervised weight reduction programme including 8 week very low energy diet.Body weight, morning peak expiratory flow (PEF), forced vital capacity (FVC), forced expiratory volume in one second (FEV(1)); and also asthma symptoms, number of acute episodes, courses of oral steroids, health status (quality of life).At the end of the weight reducing programme, the participants in the treatment group had lost a mean of 14.5% of their pretreatment weight, the controls 0.3%. The corresponding figures after one year were 11.3% and a weight gain of 2.2%. After the 8 week dieting period the difference in changes in percentage of predicted FEV(1) from baseline in the treatment and control groups was 7.2% (95% confidence interval 1.9% to 12.5%, P=0. 009). The corresponding difference in the changes in FVC was 8.6% (4. 8% to 12.5%, P0.0001). After one year the differences in the changes in the two groups were still significant: 7.6% for FEV(1) (1. 5% to 13.8%, P=0.02) and 7.6% for FVC (3.5% to 11.8%, P=0.001). By the end of the weight reduction programme, reduction in dyspnoea was 13 mm (on a visual analogue scale 0 mm to 100 mm) in the treatment group and 1 mm in the control group (P=0.02). The reduction of rescue medication was 1.2 and 0.1 doses respectively (P=0.03). After one year the differences in the changes between the two groups were -12 for symptom scores (range -1 to -22, P=0.04) and -10 for total scores (-18 to -1, P=0.02). The median number of exacerbations in the treatment group was 1 (0-4) and in the controls 4 (0-7), P=0.001.Weight reduction in obese patients with asthma improves lung function, symptoms, morbidity, and health status.

Objective: To investigate if markers of exposure to foodborne and orofecal microbes versus airborne viruses are associated with atopy and respiratory allergies. Design: Retrospective case-control study. Participants: 240 atopic cases and 240 non-atopic controls from a population sample of 1659 participants, all Italian male cadets aged 17-24. Setting: Air force school in Caserta, Italy. Main outcome measures: Serology for Toxoplasma gondii, Helicobacter pylori, hepatitis A virus, measles, mumps, rubella, chickenpox, cytomegalovirus, and herpes simplex virus type 1; skin sensitisation and IgE antibodies to relevant airborne allergens; total IgE concentration; and diagnosis of allergic asthma or rhinitis. Results: Compared with controls there was a lower prevalence of T gondii (26% v 18%, P=0.027), hepatitis A virus (30% v 16%, P=0.004), and H pylori (18%v 15%, P=0.325) in atopic participants. Adjusted odds ratios of atopy decreased with a gradient of exposure to H pylori, T gondii, and hepatitis A virus (none, odds ratio 1; one, 0.70; two or three, 0.37; P for trend=0.000045) but not with cumulative exposure to the other viruses. Conversely, total IgE concentration was not independently associated with any infection. Allergic asthma was rare (1/245, 0.4%) and allergic rhinitis infrequent (16/245, 7%) among the participants (245/1659) exposed to at least two orofecal and foodborne infections (H pylori, T gondii, hepatitis A virus). Conclusion: Respiratory allergy is less frequent in people heavily exposed to orofecal and foodborne microbes. Hygiene and a westernised, semisterile diet may facilitate atopy by influencing the overall pattern of commensals and pathogens that stimulate the gut associated lymphoid tissue thus contributing to the epidemic of allergic asthma and rhinitis in developed countries.

OBJECTIVES—To assess the prevalence of enzyme sensitisation in the detergent industry. METHODS—A cross sectional study was conducted in a detergent factory. Sensitisation to enzymes was examined by skin prick and radioallergosorbent (RAST) tests. 76 Workers were tested; 40 in manufacturing, packing, and maintenance, and 36 non-exposed people in management and sales departments. The workers were interviewed for work related respiratory and skin symptoms. Total dust concentrations were measured by a gravimetric method, and the concentration of protease in air by a catalytic method. RESULTS—Nine workers (22%) were sensitised to enzymes in the exposed group of 40, whereas none were sensitised in the non-exposed group. All the sensitised people had symptoms at work; all had rhinitis and one had asthma. Protease concentrations were generally 1 µg/m3 in the mixing area. CONCLUSION—Despite the use of encapsulated enzyme preparations, high enzyme concentrations in workplace air are possible, resulting in a higher risk of sensitisation than expected. Keywords: detergent enzymes; occupational exposure; allergy

OBJECTIVES—To characterise irritant and allergic airway responses and assess changes in forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) relative to exposure to toluene di-isocyanate (TDI). METHODS—Employees (n=313) ever assigned to a TDI production unit for ⩾3 months (1967-92) were identified from personnel records along with 158 frequency matched referents without known exposure to TDI. Reports made during visits to the occupational clinic of incidents related to exposure to TDI and annual periodic examination results (questionnaire, physical findings, and spirometry) were abstracted and assessed relative to industrial hygiene estimates of exposure to TDI. RESULTS—Mean 8 hour time weighted average estimates of TDI concentrations ranged from 9.9 ppb in jobs with potentially high exposure during the early years of plant operations to 0.5 ppb in jobs with potentially low exposure in more recent years. The corresponding rates of visits to the clinic due to incidents of exposure to TDI (including both irritant and allergic airway responses) declined from 20.5 to 1.0 visits per 100 years of employment at the unit. The annual incidence of asthma induced by TDI declined from 1.8% before 1980 to 0.7% afterwards. Neither cross sectional nor longitudinal analyses of FVC and FEV1 showed significant dose-response findings relative to exposure to TDI across the total exposed population. Among cases of occupational asthma there was an apparent initial decline in FEV1 within 2 years of first reporting symptoms, but not an accelerated rate of decline in follow up tests from 4-30 years after induction of asthma. CONCLUSIONS—Occurrences of both asthma induced by TDI and irritant airway responses due to exposure to TDI were found in this cohort, but there was no relation between cumulative exposure to TDI and irreversible airflow obstruction as assessed by spirometry. Keywords: toluene di-isocyanate; lung function decrement; occupational asthma

If asthma is due to work exposures there must be a relation between these exposures and the asthma. Asthma causes airway hyperresponsiveness and obstruction; the obstruction can be measured with portable meters, which usually measure peak expiratory flow, or sometimes forced expiratory volume in 1 second (FEV1). These can be measured serially (for instance 2 hourly) over several weeks at and away from work. Once occupational asthma develops, the asthma will be induced by many non-specific triggers common to non-occupational asthma. The challenge is to identify changes in peak expiratory flow due to work among other non-occupational causes. Standard statistical tests have been found to be insensitive or non-specific, principally because of the variable period for deterioration to occur after exposure, and the sometimes prolonged time for recovery to occur, such that days away from work may initially have lower measurements than days at work. A computer assisted diagnostic aid (Oasys) has been developed to separate occupational from non-occupational causes of airflow obstruction. Oasys-2 is based on a discriminant analysis, and achieved a sensitivity of 75% and a specificity of at least 94%; therefore peak expiratory flow monitoring combined with Oasys-2 analysis is better to confirm than to exclude occupational asthma. A neural network version in development has improved on this. Both have been based on expert interpretation of peak flow measurements plotted as daily maximum, mean, and minimum, with the first reading at work taken as the first reading of the day. Oasys has been evaluated with independent criteria against measurements made in a wide range of occupational situations. Oasys is sufficiently developed to be the initial method for the confirmation, although less so for exclusion of occupational asthma.

Objectives: To investigate the association between the duration of exclusive breast feeding and the development of asthma related outcomes in children at age 6 years. Design: Prospective cohort study. Setting: Western Australia. Subjects: 2187 children ascertained through antenatal clinics at the major tertiary obstetric hospital in Perth and followed to age 6 years. Main outcome measures: Unconditional logistic regression to model the association between duration of exclusive breast feeding and outcomes related to asthma or atopy at 6 years of age, allowing for several important confounders: sex, gestational age, smoking in the household, and early childcare. Results: After adjustment for confounders, the introduction of milk other than breast milk before 4 months of age was a significant risk factor for all asthma and atopy related outcomes in children aged 6 years: asthma diagnosed by a doctor (odds ratio 1.25, 95% confidence interval 1.02 to 1.52); wheeze three or more times since 1 year of age (1.41, 1.14 to 1.76); wheeze in the past year (1.31, 1.05 to 1.64); sleep disturbance due to wheeze within the past year (1.42, 1.07 to 1.89); age when doctor diagnosed asthma (hazard ratio 1.22, 1.03 to 1.43); age at first wheeze (1.36, 1.17 to 1.59); and positive skin prick test reaction to at least one common aeroallergen (1.30, 1.04 to 1.61). Conclusion: A significant reduction in the risk of childhood asthma at age 6 years occurs if exclusive breast feeding is continued for at least the 4 months after birth. These findings are important for our understanding of the cause of childhood asthma and suggest that public health interventions to optimise breast feeding may help to reduce the community burden of childhood asthma and its associated traits. #### Key messages

BACKGROUND: To assess the frequency of chronic upper airways symptoms and to relate the presence of these symptoms to accidental exposure to chlorine and changes in lower airways symptoms, airway function, and bronchial responsiveness in a cohort of workers at risk of sporadic occupational exposure to high concentrations of chlorine. METHODS: Data were collected on symptom assessment, spirometry, and methacholine challenge tests from 211 workers seen twice at a 2 year interval (1992- 4). RESULTS: The proportion of workers reporting chronic rhinitis was 46.9% in 1992 and 42.2% in 1994. Chronic rhinitis reported in 1994 was significantly associated with acute exposure to chlorine (self reports, p = 0.02; first aid reports, p = 0.001). In a multivariate logistic regression analysis the presence of reported accidents at the first aid unit (one accident, odds ratio (OR) 3.1, 95% confidence interval (95% CI) 1.3 to 7.5; two or more accidents, OR 6.2, 1.1 to 35.8) and of personal atopy (OR 5.5, 2.2 to 10.8) were significant predictors of chronic rhinitis in 1994. Chronic lower airways symptoms were more frequent in 1994 among workers reporting chronic rhinitis on both assessments than in others (p = 0.03) and changes in bronchial responsiveness were more pronounced in those with persistent rhinitis (p = 0.09). CONCLUSIONS: These results suggest that persistent nasal symptoms in workers at risk of reactive airways dysfunction syndrome could be a useful marker of lower respiratory tract abnormalities.

Objectives: To examine the relation between pertussis vaccination and the prevalence of wheezing illnesses in young children. Design: Prospective cohort study. Setting: Three former health districts comprising Avon Health Authority. Subjects: 9444 of 14 138 children enrolled in the Avon longitudinal study of pregnancy and childhood and for whom data on wheezing symptoms, vaccination status, and 15 environmental and biological variables were available. Main outcome measures: Episodes of wheezing from birth to 6 months, 7-18 months, 19-30 months, and 31-42 months. These time periods were used to derive five categories of wheezing illness: early wheezing (not after 18 months); late onset wheezing (after 18 months); persistent wheezing (at every time period); recurrent wheezing (any combination of two or more episodes for each period); and intermittent wheezing (any combination of single episodes of reported wheezing). These categories were stratified according to parental self reported asthma or allergy. Results: Unadjusted comparisons of the defined wheezing illnesses in vaccinated and non-vaccinated children showed no significant association between pertussis vaccination and any of the wheezing outcomes regardless of stratification for parental asthma or allergy. Wheeze was more common in non-vaccinated children at 18 months, and there was a tendency for late onset wheezing to be associated with non-vaccination in children whose parents did not have asthma, but this was not significant. After adjustment for environmental and biological variables, logistic regression analyses showed no significant increased relative risk for any of the wheezing outcomes in vaccinated children: early wheezing (0.99, 95% confidence interval 0.80 to 1.23), late onset wheezing (0.85, 0.69 to 1.05), persistent wheezing (0.91, 0.47 to 1.79), recurrent wheezing (0.96, 0.72 to 1.26), and intermittent wheezing (1.06, 0.81 to 1.37). Conclusions: No evidence was found that pertussis vaccination increases the risk of wheezing illnesses in young children. Further follow up of this population with objective measurement of allergy and bronchial responsiveness is planned to confirm these observations.

Acute bronchitis is a common disorder1usually assumed to be caused by a viral infection2with no beneficial effect resulting from antibiotic treatment.3 We examined whether acute bronchitis in a healthy individual should be regarded as an isolated event or a predictor of chronic lung disorders that has not yet clearly manifested itself clinically—that is, as bronchial hyperresponsiveness, asthma, or chronic bronchitis. In a previous study on the aetiology of acute bronchitis among adults in Gardabaer (7800 inhabitants), a suburban town south of Reykjavik, all patients diagnosed with acute bronchitis were included.4 The definition of acute bronchitis in that study was: cough (with or without expectoration) and rhonchi or coarse rales on auscultation in patients without any known underlying lung disease (according to the patients' medical records) or clinical signs of pneumonia. That prospective …

OBJECTIVES: To investigate the relation between traffic indicators in the area of residence and the occurrence of chronic respiratory disorders in children. METHODS: A population based survey was conducted in 10 areas of northern and central Italy (autumn 1994 to winter 1995) in two age groups (6-7 and 13-14 years). Information on several respiratory disorders and on traffic near residences was collected with a questionnaire given to children and to their parents. The sample analysed included 39,275 subjects (response rate 94.4%). Outcomes were: (a) early (first 2 years of life) respiratory diseases, and (b) current respiratory disorders (asthma, wheeze, cough, or phlegm in the past year). Odds ratios (ORs) and 95% confidence intervals (95% CIs), adjusted for several potential confounders, were estimated from logistic regression models. Main results were stratified by level of urbanisation (metropolitan areas, other centres). RESULTS: In the metropolitan areas, high frequency of lorry traffic in the street of residence was associated with significantly increased risks for many adverse respiratory outcomes. Among early respiratory diseases, the strongest associations were found for recurrent bronchitis (OR 1.69, 95% CI 1.24 to 2.30), bronchiolitis (1.74, 1.09 to 2.77) and pneumonia (1.84, 1.27 to 2.65), although no association was detected for episodes of wheezing bronchitis. All the current respiratory disorders were positively and consistently associated with frequency of lorry traffic, particularly the most severe bronchitic and wheezing symptoms: persistent phelgm for > 2 months (1.68; 1.14 to 2.48), and severe wheeze limiting speech (1.86; 1.26 to 2.73). No or weaker associations with heavy vehicular traffic were detected in urban and rural areas and no increased risks were found in the whole sample with the reported traffic density in the zone of residence. After extensive evaluations, the potential of reporting bias seems unlikely. CONCLUSION: Exposure to exhausts from heavy vehicular traffic may have several adverse effects on respiratory health of children living in metropolitan areas, increasing the occurrence of lower respiratory tract infections early in life and of wheezing and bronchitic symptoms at school age.

Objectives—Questionnaires, lung function tests, and peak flow measurements are widely used in occupational health care to screen for subjects with respiratory disease. However, the diagnostic performance of these tests is often poor. Application of these tests in a stepwise manner would presumably result in a better characterisation of subjects with respiratory disease. Methods—Cross sectional data from workers exposed to acid anhydrides, to laboratory animals,and toflour dusts were used. Sensitivity and specificity were calculated from cross tables of diVerent (combinations of) tests for bronchial hyperresponsiveness and bronchial irritability in the past four weeks (BIS). From sensitivity and specificity likelihood ratios were computed and change in probability of BIS was calculated. Results—The prevalence of BIS was 7%, 7%, and 5%, respectively. In all groups questionnaire data provided excellent sensitivity but poor specificity, which was inherent on the broad definition of symptoms. Adding the forced expiratory volume in one second/forced vital capacity (FEV1/FVC) ratio yields almost perfect specificity, and peak expiratory flow (PEF) variability is intermediate in populations in which smoking induced or non-allergic respiratory diseases predominates. In occupational groups in which asthma is a problem, adding PEF measurements will optimise sensitivity and specificity in detection of BIS. The probability of BIS for subjects with a negative combined test outcome was lower than the probability before testing. Subjects with a positive combined test outcome had a probability of BIS after the tests at least three times the probability before. Conclusions—Combined testing yields better sensitivity and specificity.An advantage of combined testing is an economy in the eVort to screen for subjects with BIS. Combined testing resulted in more detailed estimation of the probability of BIS. (Occup Environ Med 1998;55:119‐125)

BACKGROUND: Regular inhaled beta 2 agonist therapy is associated with loss of bronchoprotection to indirect bronchial provocation challenges such as allergen or adenosine monophosphate (AMP), while directly acting challenge is less affected, implying preferential mast cell tolerance. Glucocorticosteroids may reverse such beta 2 adrenoreceptor tolerance and upregulate mast cell beta 2 adrenoceptor function. METHODS: The effect of single high dose glucocorticosteroids on terbutaline induced loss of bronchoprotection was studied in a placebo controlled, double blind, cross-over study. Fifteen asthmatic subjects who were not taking inhaled glucocorticosteroids underwent two 10-day treatment periods with terbutaline (500 micrograms four times daily via Turbohaler), each followed by a single dose of inhaled budesonide (800 micrograms via Turbohaler) or identical placebo. RESULTS: Regular treatment with terbutaline resulted in significant loss of bronchoprotection to AMP (mean difference (95% CI) -1.7 (-3.0 to 0.4) doubling dilutions) but not to methacholine (mean difference -0.1 (-1.0 to 0.8) doubling dilutions). Single high dose budesonide increased the protective effect of terbutaline more to AMP than to methacholine challenge (+0.76 (0.3) doubling dilutions compared with +0.13 (0.4) doubling dilutions, respectively). The mean (SE) difference between budesonide and placebo for methacholine challenge was 0.08 (0.14) whereas that for AMP was 0.075 (0.15); p = NS. The difference in PC20 was not statistically significant when compared with placebo for either challenge agent. CONCLUSIONS: Inhaled glucocorticosteroids in a single dose had no significant effect in restoring terbutaline induced loss of bronchoprotection, implying that mast cell beta 2 adrenoceptor sensitivity is not restored by a single dose of an inhaled glucocorticosteroid in asthma.

BACKGROUND: A study was undertaken to test the hypothesis that airway calibre may alter lung deposition and therefore lung bioavailability of inhaled drugs as a result of narrowed airways reducing peripheral drug delivery. This was evaluated using the early lung absorption profile of salbutamol over the first 30 minutes after inhalation. METHODS: Three groups were compared: (1) 10 normal subjects with mean forced expiratory volume in one second (FEV1) 109.5% predicted and mid forced expiratory flow (FEF25-75) 103.0%, (2) 10 mild asthmatic patients with FEV1 102.0% and FEF25-75 82.6%, and (3) 10 severe asthmatic patients with FEV1 49.2% and FEF25-75 27.5% predicted. Each subject had one study visit where a single dose of nebulised salbutamol was given (40 micrograms/kg) via a Ventstream nebuliser with mouthpiece followed by mouth rinsing. Plasma salbutamol levels were measured at five, 10, 20, and 30 minutes after the end of nebulisation with calculation of maximal (Cmax) and average (Cav) concentration over 0-30 minutes. Systemic beta 2 responses (plasma potassium, tremor and heart rate) and airway responses (FEV1, FEF25-75) were measured before and 30 minutes after nebulisation. RESULTS: For Cav over 0-30 minutes the severe asthmatic patients had a lower plasma salbutamol concentration (1.31 ng/ml) than either the normal subjects (2.40 ng/ml) or those with mild asthma (2.45 ng/ml): normal subjects versus severe asthmatics 95% CI 0.30 to 1.88, mild versus severe asthmatics 95% CI 0.07 to 2.21. Airway responses as delta FEF25-75 were lower in the severe asthmatic subjects (0.30 l/s) than in either the normal subjects (0.69 l/s) or those with mild asthma (0.74 l/s): normal subjects versus severe asthmatic subjects 95% CI 0.09 to 0.88, mild versus severe asthmatics 95% CI 0.04 to 0.93. Values for delta log tremor also showed attenuated responses in those with severe asthma (1.22 mg2/s) compared with normal subjects (2.00 mg2/s) or those with mild asthma (2.02 mg2/s): normal subjects versus those with severe asthma 95% CI -0.02 to 3.30, mild versus severe asthmatics 95% CI 0.02 to 3.30. CONCLUSIONS: These results show that baseline airway calibre significantly alters the early lung absorption profile of salbutamol in patients with severe asthma. This may have implications in terms of optimising dose and delivery of inhaled beta 2 agonists in these patients.

BACKGROUND: The role of platelet activating factor (PAF) in asthma remains controversial. The priming effect of PAF on leukotriene B4 (LTB4) release, 5-lipoxygenase activity, and intracellular calcium levels in asthmatic neutrophils was examined. METHODS: LTB4 and other lipoxygenase metabolites in neutrophils obtained from 17 asthmatic patients and 15 control subjects were measured by reverse phase-high performance liquid chromatography (RP-HPLC). Intracellular calcium levels were monitored using the fluorescent probe fura-2. RESULTS: The mean (SD) basal LTB4, release from neutrophils was not significantly different between the two groups (0.05 (0.01) vs 0.03 (0.02) ng/10(6) cells); however, when stimulated with calcium ionophore A23187 (2.5 microM), neutrophils from asthma patients released more LTB4 than cells from control subjects (15.7 (1.2) vs 9.9 (1.6) ng/10(6) cells). Although PAF alone did not alter LTB4 release, it enhanced the response to subsequent A23187 stimulation. This effect was observed following treatment for five minutes with PAF at concentrations > 1.0 microM. The maximal effect was seen with 5.0 microM PAF + 2.5 microM A23187 (62.7 (2.2) vs 18.6 (2.3) ng/10(6) cells). Pretreatment with PAF also increased 5-lipoxygenase activity and intracellular calcium levels in neutrophils from asthmatic patients to a greater extent than in those from non-asthmatic patients. CONCLUSIONS: These findings indicate that, in neutrophils from asthmatic patients, PAF enhances LTB4 release and increases 5-lipoxygenase activity and intracellular calcium to a greater extent than in neutrophils from non-asthmatic patients.

BACKGROUND: A study was undertaken to determine whether montelukast, a new potent cysteinyl leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction. The relationship between the urinary excretion of LTE4 and exercise-induced bronchoconstriction was also investigated. METHODS: Nineteen non-smoking asthmatic patients with a forced expiratory volume in one second (FEV1) of > or = 65% of the predicted value and a reproducible fall in FEV1 after exercise of at least 20% were enrolled. Subjects received placebo and montelukast 100 mg once daily in the evening or 50 mg twice daily, each for two days, in a three-period, randomised, double blind, crossover design. In the evening, approximately 20-24 hours after the once daily dose or 12 hours after the twice daily dose, a standardised exercise challenge was performed. Data from 14 patients were available for complete analysis. RESULTS: The mean (SD) maximal percentage decrease in FEV1 after exercise was 29.6 (16.0), 17.1 (8.2), and 14.0 (9.4) for placebo, once daily, and twice daily regimens, respectively. The mean (95% CI) percentage protection was 37 (15 to 59) for the group who received 50 mg twice daily and 50 (31 to 69) for those who received 100 mg once daily. Active treatments were not different from each other. The mean (SD) plasma concentrations of montelukast were higher after the twice daily regimen (1.27 (0.81) microgram/ml) than after the once daily regimen (0.12 (0.09) microgram/ml); there was no correlation between the percentage protection against exercise-induced bronchoconstriction and plasma concentrations. After exercise urinary excretion of LTE4 increased significantly during placebo treatment (from 34.3 to 73.7 pg/mg creatinine; p < 0.05) but did not correlate with the extent of exercise-induced bronchoconstriction. CONCLUSIONS: Montelukast protects similarly against exercise-induced bronchoconstriction between plasma concentrations of 0.12 and 1.27 micrograms/ml. The increase in the urinary excretion of LTE4 after exercise and the protection from exercise-induced bronchoconstriction with a cysteinyl leukotriene receptor antagonist provide further evidence of the role of leukotrienes in the pathogenesis of exercise-induced bronchoconstriction.

BACKGROUND: Previous studies evaluating spirometric values and symptoms have shown that once daily theophylline administered in the evening produces greater stabilisation of the airway function in asthmatic patients than the prototype theophylline given twice a day. The aim of this study was to compare the effects on bronchial responsiveness to methacholine of an ultrasustained release theophylline formulation (Diffumal-24, Malesci, Florence, Italy) administered once a day, a sustained release theophylline formulation (Theo-Dur, Recordati, Milan, Italy) administered twice a day, and placebo. METHODS: The study was performed in 12 adult patients with asthma using a randomised, double blind, three phase, cross-over design. Each phase lasted seven days and was followed or preceded by at least three days of theophylline washout. Diffumal-24 was administered once a day at 20.00 hours whereas Theo-Dur was given twice a day at 08.00 hours and 20.00 hours. In each patient the total daily dose of theophylline was the same during both phases. The dose of the two active preparations was titrated to individual needs before the beginning of the study and then given in divided or once daily doses. At 08.00, 14.00, and 20.00 hours on day 7 of each phase serum theophylline concentrations were measured and spirometric tests (FEV1) and bronchial challenge with methacholine were also performed. RESULTS: When the administration of Diffumal-24 was compared with that of Theo-Dur, a higher serum theophylline concentration of the former was seen in the morning whereas at 20.00 hours the reverse was true. Compared with placebo, at 08.00 hours Diffumal-24 improved FEV1 whereas Theo-Dur did not (difference between treatments 0.29 1, 95% CI 0.12 to 0.45). At 08.00 hours Diffumal-24 decreased bronchial sensitivity to methacholine, expressed as a natural logarithm of PD20, to a greater extent than Theo-Dur (difference between treatments 0.54 log units, 95% CI 0.016 to 1.08). The morning advantage observed with Diffumal-24 administration was not associated with a deterioration in the state of the airway during the daytime, the protective activity against methacholine during the 12 hours of the monitoring period being constant. Furthermore there was no difference in the mean FEV1 between the two treatments at 14.00 and 20.00 hours. CONCLUSIONS: In adults with stable bronchial asthma treatment with a single dose of Diffumal-24 administered in the evening improved airflow obstruction and reduced bronchial hyperresponsiveness.

BACKGROUND: There is increasing evidence that wheezing during childhood may be a heterogeneous condition, and that different forms of wheezing may be associated with different risk factors and prognosis. The aim of this study was to determine if measures of airway lability and of atopy could identify distinct wheezing phenotypes during childhood. METHOD: In a cohort of children followed from birth peak flow variability (n = 600) was evaluated and methacholine challenge responsiveness (n = 397) was measured at age 11 in relation to wheezing before the age of three, and at age six and 11 years total serum IgE and skin test reactivity to allergens were determined. RESULTS: Neither positive peak flow variability nor methacholine hyperresponsiveness measured at age 11 were associated with wheezing occurring only during the first three years of life. Both methacholine hyperresponsiveness and positive peak flow variability were associated with wheezing at both ages six and 11 (OR 5.1 (95% CI 2.4 to 10.6) and 2.3 (1.2 to 4.5), respectively). In addition, positive peak flow variability was associated with wheezing up to the age of six but not at age 11 in non-atopic children (OR 2.9 (95% CI 1.0 to 8.8)). Methacholine hyperresponsiveness measured at age 11 was more frequently observed in boys (OR 2.1 (95% CI 1.2 to 3.5)) and was strongly associated with serum IgE levels measured at ages six and 11 (p < 0.001) and with positive skin test reactivity (OR 4.5 (95% CI 2.0 to 10.1)). Peak flow variability was unrelated to sex or markers of atopy (IgE and skin test reactivity). CONCLUSIONS: Methacholine responsiveness and peak flow variability assessed at age 11, together with markers of atopy (IgE and skin test reactivity to allergens) identify three different wheezing phenotypes in childhood: "transient early wheezing" limited to the first three years of life and unrelated to increased airway lability; "non-atopic wheezing" of the toddler and early school years associated with positive peak flow variability but not with methacholine hyperresponsiveness; and "IgE-associated wheeze/asthma" associated with persistent wheezing at any age and with methacholine hyperresponsiveness, peak flow variability, and markers of atopy.

BACKGROUND: Childhood asthma and wheeze only in the presence of respiratory infection (wheezy bronchitis) appear to have different prognoses and may differ in their aetiology and heritability. In particular, slight reductions in lung function may be associated with episodes of wheezing associated with intercurrent viral infection. METHODS: Outcomes for wheezing symptoms and lung function were studied in 133 offspring of three distinct groups of 69 middle aged probands with childhood histories of (1) atopic asthma (n = 18), (2) wheeze associated with upper respiratory tract infection (wheezy bronchitis, n = 24), and (3) no symptoms (n = 27). Probands were selected from a previously studied cohort in which outcomes of wheezy bronchitis and asthma had been shown to differ. RESULTS: Children of probands with wheezy bronchitis had a lower prevalence of current wheezing symptoms. Forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) in boys of probands with a history of wheezy bronchitis were significantly reduced compared with either of the other two groups (p < 0.0001). In a multivariate analysis, grouping based on parent proband had a significant effect on lung function, independent of factors such as symptoms, atopy or smoking history. CONCLUSIONS: The different symptomatic and lung function outcome in children of probands with wheezy bronchitis and asthma provides further evidence that wheezy bronchitis and asthma differ in their natural history and heritability, and suggests that there may be familial factors specific to each wheezing syndrome.

BACKGROUND: Salbutamol is the most widely prescribed short acting beta 2 agonist and salmeterol is the first long acting inhaled beta 2 agonist. The dose equivalence of salmeterol and salbutamol is disputed. Estimates of weight-for-weight dose ratio have ranged from 1:2 to 1:16. A study was undertaken to clarify the true dose ratio. METHODS: The bronchoprotection afforded against repeated methacholine challenge by inhaled salmeterol 25 micrograms and 100 micrograms and salbutamol 100 micrograms and 400 micrograms was compared in a randomised, double blind, placebo controlled, crossover trial. Subjects were 16 stable asthmatics with a baseline forced expiratory volume in one second (FEV1) of > or = 65% predicted, screening concentration provoking a fall in FEV1 of 20% (PC20FEV1) of < or = 8mg/ml, and a shift in PC20FEV1 of more than two doubling concentration steps following inhalation of salbutamol 400 micrograms. On five separate occasions subjects underwent methacholine challenge before and 30 and 120 minutes after drug administration. PD20FEV1 was calculated for each challenge. FEV1 at 90 minutes after drug administration was also recorded. RESULTS: Bronchoprotection afforded by salmeterol was increased at 120 minutes compared with 30 minutes and protection by salbutamol was decreased. Protection by both doses of salmeterol was similar to salbutamol 100 micrograms at 30 minutes but significantly greater at 120 minutes. FEV1 at 90 minutes was significantly greater after salmeterol 100 micrograms than after placebo, but there were no other significant differences between treatments. Maximal observed protection was equivalent for salmeterol 100 micrograms and salbutamol 400 micrograms. CONCLUSIONS: The data are compatible with a weight-for- weight dose ratio for salmeterol:salbutamol of < or = 1:4.

BACKGROUND: Bone mineral density has been reduced in patients with asthma taking inhaled corticosteroids in some cross sectional studies and this could be important if treatment is continued for several decades. The possibility of confounding by age, menopausal status, physical activity and, especially, past oral steroid use has not been excluded in most studies. The present study was designed to assess the magnitude of any reduction in bone mineral density in relation to inhaled steroid use after adjusting for these factors. METHODS: Bone mineral density (BMD), vertebral fractures, and markers of bone metabolism (serum osteocalcin, procollagen peptide I, bone-specific alkaline phosphatase, and urinary deoxypyridinoline cross links) were measured in 81 patients with asthma age 20-40 years; 34 patients (19 men) who had never had inhaled or systemic steroids and 47 (19 men) who had taken inhaled steroids for at least five years with limited exposure to systemic steroids in the past. Data relating to past medication use, physical activity, smoking, and other confounding factors were collected by questionnaire. The relation between inhaled steroid dose and duration and BMD was assessed by linear regression analysis, accounting for potential confounders including weight, exercise, and oral steroid use. RESULTS: The 47 patients taking an inhaled steroid had a mean current dose of 620 micrograms/day (range 100-3000 micrograms), a mean duration of use of 7.8 years, and had had a mean of 0.85 courses of prednisolone in the past. There was no significant difference in mean BMD values between those who were and those who were not on inhaled steroids in men or women. However, on multivariate analysis, cumulative inhaled steroid dose was associated with a reduction in posterior-anterior (P-A) and lateral lumbar spine bone mineral density in women, equivalent to a 0.11 standard deviation reduction in bone density per 1000 micrograms/day inhaled steroid per year after adjustment for potential confounding factors (95% CI for P-A spine 0.01 to 0.22; for lateral spine 0.02 to 0.21). Previous oral steroid use was not an important confounding factor in these patients. Inhaled steroid use was not related to BMD at the wrist or hip in women or at any skeletal site in men. Women taking an inhaled steroid had lower levels of serum osteocalcin than those not taking them, although this was not dose related. Inhaled steroid use was not associated with differences in other markers of bone metabolism in men or women or with the presence of vertebral fractures. CONCLUSIONS: Although an effect of confounding factors cannot be excluded entirely in a cross sectional study, our findings are in keeping with an effect of inhaled steroid therapy in reducing bone density in the spine in women and provide an estimate of the magnitude of this effect.

BACKGROUND: Commercially available salbutamol is a racemic mixture consisting of equal amounts of the two enantiomers, R-salbutamol and S- salbutamol, felt to be active and inert, respectively. METHODS: A double blind, randomised, four way, crossover study was performed in 12 well controlled asthmatic subjects (forced expiratory volume in one second (FEV1) > 70% predicted, no beta 2 agonists for > or = 4 weeks). Subjects were studied on four days at intervals of 48 hours to seven days. FEV1 was assessed before and both FEV1 and methacholine PC20 were measured 20 and 180 minutes after a single dose of nebulised racemic salbutamol 2.5 mg, R-salbutamol 1.25 mg, S-salbutamol 1.25 mg, and placebo. RESULTS: Equivalent bronchodilation was seen for both R- salbutamol and racemic salbutamol (mean (SE) 12.4 (3.1)% and 12.0 (3.0)%, respectively, at 20 minutes and 5.9 (2.9)% and 5.2 (2.2)% at 180 minutes). The increase in FEV1 of 5.2 (0.9)% at 20 minutes and the decline in FEV1 of 2.9 (2.1)% at 180 minutes after S-salbutamol were not significantly different from the placebo response. Compared with placebo the methacholine PC20 after R-salbutamol and racemic salbutamol improved by 3.3 (95% CI 2.5 to 4.1) and 3.4 (95% CI 2.6 to 4.2) doubling doses, respectively, at 20 minutes and 1.2 (95% CI 0.6 to 1.8) and 1.0 (95% CI 0.2 to 1.8) doubling doses at 180 minutes. S-salbutamol resulted in an improvement of 0.9 (95% CI 0.3 to 1.5) doubling doses at 20 minutes and no change at 180 minutes. Restlessness (n = 11) and increased pulse were seen 20 minutes after racemic and R-salbutamol but not S-salbutamol or placebo, and not at 180 minutes. There were no other adverse events. CONCLUSION: A single dose of 1.25 mg nebulised R- salbutamol produced equivalent bronchoprotection, bronchodilation, restlessness, and tachycardia as did 2.5 mg of racemic salbutamol. S- salbutamol 1.25 mg had a weak bronchoprotective effect; this could be because of a small amount of contamination with R-salbutamol or because S-salbutamol is an intrinsically weak beta 2 receptor stimulant.

BACKGROUND: Inhaled propranolol causes bronchoconstriction in asthmatic subjects by an indirect mechanism which remains unclear. Inhaled frusemide has been shown to attenuate a number of indirectly acting bronchoconstrictor challenges. The aim of this study was to investigate whether frusemide could protect against propranolol-induced bronchoconstriction in patients with stable mild asthma. METHODS: Twelve asthmatic subjects were studied on three separate days. At the first visit subjects inhaled increasing doubling concentrations of propranolol (0.25-32 mg/ml), breathing tidally from a jet nebuliser. The provocative concentration of propranolol causing a 20% reduction in FEV1 (PC20FEV1 propranolol) was determined from the log concentration- response curve for each subject. At the following visits nebulised frusemide (4 ml x 10 mg/ml) or placebo (isotonic saline) was administered in a randomised, double blind, crossover fashion. FEV1 was measured immediately before and five minutes after drug administration. Individual PC20FEV1 propranolol was then administered and FEV1 was recorded at five minute intervals for 15 minutes. Residual bronchoconstriction was reversed with nebulised salbutamol. RESULTS: Frusemide had no acute bronchodilator effect but significantly reduced the maximum fall in FEV1 due to propranolol: mean fall 18.2% after placebo and 11.8% after frusemide. The median difference in maximum % fall in FEV1 within individuals between study days was 3.6% (95% CI 1.2 to 11.7). CONCLUSIONS: Frusemide attenuates propranolol-induced bronchoconstriction, a property shared with sodium cromoglycate. Both drugs block other indirect challenges and the present study lends further support to the suggestion that frusemide and cromoglycate share a similar mechanism of action in the airways.

BACKGROUND: Cough is a major symptom in some children with asthma. The relationship between cough and the severity of asthma is ill defined. A study was undertaken to test the hypotheses that, in children with asthma who cough as a major part of their asthma symptoms, cough receptor sensitivity (CRS) is heightened during an acute severe exacerbation of asthma but not in the non-acute phase and airway calibre or its change correlates with CRS. METHODS: Spirometric measurements and the capsaicin CRS test were performed on children admitted to hospital for an acute severe exacerbation of asthma. Nasal secretions were tested for viruses. The children were grouped into those who usually cough with asthma episodes and those who do not. The tests were repeated 7-10 days and 4-6 weeks later. The CRS outcome measure used was the concentration of capsaicin required to stimulate two (Cth) and five coughs (C5). RESULTS: The CRS of the group who coughed (n = 15) was significantly higher than those who did not cough (n = 16) (mean difference log Cth 0.77 mumol (95% CI 0.35 to 1.18), C5 0.72 mumol (95% CI 0.26 to 1.18)) during acute asthma but not after the exacerbation. CRS was not significantly different between groups based on the presence of a viral infection. Neither forced expiratory volume in one second (FEV1) nor its change correlated with CRS nor its change. CONCLUSIONS: In children with asthma CRS is heightened in acute severe asthma in the subgroup of children who have cough as a significant symptom with their asthma episodes. In acute and non-acute asthma CRS does not correlate with FEV1.

BACKGROUND: Leukotriene receptor antagonists have been shown to protect against bronchoconstriction induced by antigens, exercise, and cold air. There are relatively few clinical studies reported in patients with asthma. The present study is the first clinical evaluation of pranlukast (SB 205312, ONO-1078) outside Japan in patients with asthma. METHODS: A randomised, double blind, placebo controlled, parallel group, multicentre four week study of the safety and tolerability of oral pranlukast, 225 or 337.5 mg twice daily, was performed in patients with mild to moderate asthma. Preliminary efficacy data were obtained; the main efficacy variables evaluated were forced expiratory volume in one second (FEV1) and morning domiciliary (home) peak expiratory flow rates (PEFR). Clinic PEFR and daytime and night-time asthma symptom scores were also recorded. RESULTS: Compared with the placebo group the improvement in morning home PEFR was statistically significant at all time points for patients receiving pranlukast 337.5 mg twice daily and at weeks 1 and 2 for those treated with pranlukast in a dose of 225 mg twice daily. Mean morning home PEFR increased by 10.8 to 18.61/min (95% CI 0.2 to 29.3 l/min) in patients treated with pranlukast compared with a slight deterioration in those given placebo. FEV1 significantly increased within one hour after the first dose of pranlukast compared with baseline and this increase was maintained for eight hours. Improvements in trough FEV1-that is, at the end of the dosing interval- were statistically significant for the group treated with pranlukast 225 mg twice daily compared with placebo at week 4. Mean increases in FEV1 ranged from 210 ml to 340 ml (95% CI 60 to 500 ml) at trough in the pranlukast group. Patients treated with pranlukast also showed improvements in summary symptom and night-time asthma scores. Pranlukast was well tolerated, and no drug related changes in haematological and biochemical variables were observed. CONCLUSIONS: Pranlukast, an oral leukotriene receptor antagonist, is well tolerated and is effective for the treatment of asthma. It increased FEV1 within one hour of dosing, improved patient summary symptom and night-time asthma scores, and reduced the use of rescue bronchodilators, thus providing further evidence of a role for leukotrienes in the pathogenesis of asthma.

BACKGROUND: The concentration of nitric oxide (NO) is increased in the exhaled air of patients with inflammation of the airways, suggesting that this may be a useful measurement to monitor inflammation in diseases such as asthma. However, there have been concerns that exhaled NO may be contaminated by the high concentrations of NO derived from the upper airways, and that this may account for differences in reported values of exhaled NO using different techniques. A study was performed, with argon as a tracer, to determine the extent of nasal contamination of exhaled NO using different expiratory manoeuvres. METHODS: Exhaled and nasal NO were measured by a chemiluminescence analyser. Argon (4.8%) was delivered continuously to the nose. Gas was sampled from the posterior oropharynx and argon and carbon dioxide were measured by mass spectrometry at the same time as NO. RESULTS: During a single expiration against a low resistance and during breath holding there was no evidence for nasal contamination, whereas during exhalation without resistance argon concentration in the oropharynx was increased from 0.91% (95% CI 0.84% to 0.98%) in ambient air to 1.28% (0.9% to 2.24%, p < 0.0001) during a single breath or 2.37% (2.29% to 2.51%, p < 0.0001) during tidal breathing. CONCLUSIONS: Collection of exhaled NO in a reservoir during tidal breathing is likely to be contaminated by NO derived from the nose and this may underestimate any increases in NO derived from the lower respiratory tract in inflammatory diseases. However, with slow expiration against a resistance and created back pressure to close the soft palate, there is no contamination of exhaled air which then reflects concentrations of NO in the lower airways.

BACKGROUND: The long acting beta 2 agonist formoterol has proved to be an effective bronchodilator with a prolonged action of 12-14 hours. However, the precise role of formoterol in the maintenance treatment of asthma is still under debate. A study was performed to investigate the efficacy and safety of treatment with formoterol for six months in subjects with asthma. METHODS: In a multicentre double blind, placebo controlled, parallel group study 239 subjects with mild to moderate asthma were randomly assigned to treatment with either inhaled formoterol 24 micrograms twice daily (n = 125) or placebo (n = 114) during eight months. The study consisted of a four week run in period, a 24 week treatment period, and a four week washout period. All subjects were using regular inhaled corticosteroids (100-3200 micrograms daily) but were still needing at least five inhalations of short acting beta 2 agonist per week for symptom relief. The study was performed in 10 outpatient clinics in Canada, and five outpatient clinics and one coordinating centre for 44 Dutch general practitioners in The Netherlands. Twice daily self-reported peak expiratory flow (PEF) measurements, symptom scores, and rescue beta 2 agonist use during the last 28 treatment days compared with baseline values were used as main outcome measures. Spirometric values were measured at entry, at the start of treatment, after four, 12 and 24 weeks of treatment, and after four weeks washout. RESULTS: One hundred and twenty five subjects received formoterol 24 micrograms twice daily via Turbohaler and 114 received placebo. Baseline FEV1 was 67.1% predicted and mean bronchodilator reversibility was 26%. The mean total asthma symptom score was 3.6 (maximum possible 21). A significant decrease in symptoms in favour of formoterol (difference from placebo -0.64, 95% CI -0.04 to -1.23, p = 0.04) was observed. Compared with placebo, morning PEF increased (difference from placebo 28 l/min, 95% CI 18.3 to 37.7, p = 0.0001) and the use of short acting beta 1 agonists decreased (daytime difference from placebo -1.1 inhalation, 95% CI -1.4 to -0.7, p = 0.0001) in the formoterol group. PEF returned to baseline following discontinuation of formoterol, as did asthma symptom scores. Thirty three patients treated with formoterol and 32 treated with placebo required treatment with prednisolone during the study (58 and 55 courses, respectively). CONCLUSIONS: Adding formoterol 24 micrograms twice daily by Turbohaler to inhaled corticosteroids was effective in improving symptom scores and morning PEF, and decreasing the use of rescue beta 2 agonists. There was no apparent loss of asthma control during 24 weeks of treatment with formoterol.

BACKGROUND: Accumulating evidence suggests that the cytokine network is central to the immunopathology of bronchial asthma and the existence of naturally occurring cytokine antagonists has added to this complexity. Upregulation of both interleukin 1 beta (IL-1 beta) and its naturally occurring receptor antagonist, interleukin 1 receptor antagonist (IL- 1ra), has previously been observed on asthmatic bronchial epithelium compared with normal airways. METHODS: The effect of inhaled beclomethasone dipropionate (BDP) on asthmatic bronchial epithelial expression of IL-1 beta and IL-1ra was studied. Frozen bronchial biopsy specimens from nine asthmatic subjects receiving 1000 micrograms BDP daily for eight weeks and from six asthmatic subjects receiving matching placebo were stained with anti-IL-1 beta and anti-IL-1ra antibodies. Hue-saturation-intensity (HSI) colour image analysis was used to quantify the brown immunoperoxidase reaction colour present on the bronchial epithelium. RESULTS: There was a significant twofold decrease in the epithelial expression of IL-1 beta after treatment with BDP but no significant change was seen in IL-1ra (P = 0.175). CONCLUSION: The selective inhibition of IL-1 beta, without effect on IL- 1ra, provides a novel mechanism for the anti-inflammatory action of glucocorticosteroids.

BACKGROUND: Inhaled adenosine monophosphate (AMP) is thought to cause bronchoconstriction in asthmatic patients indirectly through mast cell mediator release. It may therefore be a more sensitive marker of airway inflammation in asthma and hence more specific for epidemiological surveys of asthma than challenges that act directly on airway smooth muscle such as histamine. There is some uncertainty as to how repeatable the measurement is and this is important if it is to be used for epidemiological studies. METHODS: The response to histamine and AMP challenges and the protection afforded by terbutaline (500 micrograms) against these two challenges was measured on two occasions two weeks apart in 20 subjects with asthma (19 completed the study). The response to histamine and AMP was measured as the provocative dose causing a 20% fall in forced expiratory volume in one second (PD20) and the protection afforded by terbutaline in doubling doses (DD). Repeatability was assessed as the limits of agreement. RESULTS: Although terbutaline had a slightly greater protective effect against AMP than histamine on both the first (delta PD20 = 2.66 versus 2.11 DD) and second occasion (2.56 and 2.15 DD), the differences were not statistically significant. The limits of agreement for the two histamine and two AMP challenges after placebo were from 3.06 to -3.5 and from 3.78 to -4.54 DD respectively, and these values did not differ significantly. The agreement limits between the first PD20 histamine and PD20 AMP values after placebo were similar, being from 3.73 to - 3.72 DD after allowing for the 17.8-fold higher PD20 values for AMP compared with histamine. CONCLUSIONS: Terbutaline caused a slightly greater inhibition of the bronchoconstrictor response to AMP than histamine but the differences were small and non-significant. Any differences in repeatability between AMP and histamine challenges are small and in this study were not significant. The fact that the agreement between histamine and AMP PD20 values was similar to the agreement between repeat histamine or repeat AMP PD20 values suggests that, within an asthmatic population, PD20 AMP may not be providing different information from that provided by PD20 histamine.

BACKGROUND: Severe alpha 1-antitrypsin (AAT) deficiency (PiZZ) is associated with an increased risk of lung emphysema, especially in smokers. The aim of this study was to identify risk factors other than smoking for declining lung function. METHODS: Lung function was studied in 225 self-reported never-smoking PiZZ individuals included in the Swedish AAT deficiency register. RESULTS: Lung function was poorer in men than in women (mean (SD) forced expiratory volume in one second (FEV1) 80 (30) versus 88 (17)% predicted) despite the fact that the men were younger (mean (SD) age 45 (18) versus 51 (17) years), and poorer in those aged 50 or older than in those aged under 50 (mean (SD) FEV1 70 (30) versus 98 (16)% predicted). Self-reported occupational exposure to gas, fumes, or dust occurred more frequently in men than in women. In those aged 50 or older lung function was lower in individuals exposed to airway irritants than those who were not exposed (mean (SD) FEV1 63 (29) versus 76 (31)% predicted). Male sex, increasing age, and previous symptoms of wheezing were independent risk factors for lung function impairment, and male sex, wheeziness, and occupational exposure to airway irritants were independent risk factors in the subjects aged 50 years or more. CONCLUSIONS: In non-smoking PiZZ individuals lung function declines with increasing age, especially after 50. Men are at greater risk of lung function deterioration than women. Asthmatic symptoms and occupational exposure to airway irritants appear to constitute additional risk factors.

BACKGROUND: It has been postulated that dietary antioxidants may influence the expression of allergic diseases and asthma. To test this hypothesis a case-control study was performed, nested in a cross sectional study of a random sample of adults, to investigate the relationship between allergic disease and dietary antioxidants. METHODS: The study was performed in rural general practices in Grampian, Scotland. A validated dietary questionnaire was used to measure food intake of cases, defined, firstly, as people with seasonal allergic-type symptoms and, secondly, those with bronchial hyperreactivity confirmed by methacholine challenge, and of controls without allergic symptoms or bronchial reactivity. RESULTS: Cases with seasonal symptoms did not differ from controls except with respect to the presence of atopy and an increased risk of symptoms associated with the lowest intake of zinc. The lowest intakes of vitamin C and manganese were associated with more than fivefold increased risks of bronchial reactivity. Decreasing intakes of magnesium were also significantly associated with an increased risk of hyperreactivity. CONCLUSIONS: This study provides evidence that diet may have a modulatory effect on bronchial reactivity, and is consistent with the hypothesis that the observed reduction in antioxidant intake in the British diet over the last 25 years has been a factor in the increase in the prevalence of asthma over this period.

BACKGROUND: The perception of bronchoconstriction varies among patients with asthma and this perception may be related to the covariation of sensory and affective aspects of dyspnoea. A study was performed to evaluate whether there are differences in the perception of histamine induced bronchoconstriction between anxious and non-anxious perceivers and whether anxious perception of bronchoconstriction can be predicted by higher levels of baseline anxiety. METHODS: Seventy eight asthmatic subjects referred for a histamine challenge test undertook baseline measures for anxiety symptomatology and forced expiratory volume in one second (FEV1) followed by perceived breathlessness (Borg scale), anxiety (SUDS), and FEV1 measurement before and during induced bronchoconstriction. Based on the correlation between Borg and SUDS scores, the patients were divided into anxious and non-anxious perceivers. RESULTS: Forty one patients reported no anxiety during the challenge test. The anxious perceivers (n = 20) had higher levels of perceived breathlessness and anxiety at 20% fall in FEV1 and were more accurate in their perception of airways obstruction than non-anxious perceivers (n = 58). However, they did not report higher baseline levels of anxiety symptomatology. CONCLUSIONS: Anxiety experienced during bronchial challenge testing may result from the accurate perception of physiological changes and further direct attention to airways obstruction.

BACKGROUND: The management of asthma attacks by general practitioners in 1992/93 was compared with 1991/92 in relation to recommended guidelines. METHODS: The findings from a postal survey of 299 UK general practitioners who managed 2332 patients with an asthma attack in 1992/93 were compared with those from 218 practitioners who managed 1805 attacks in 1991/92. Management by a subgroup of practitioners from a special interest group was analysed separately. RESULTS: In 1992/93 2031 (87%) of attacks were managed entirely by general practitioners, 251 (11%) were referred for admission to hospital, and 50 (2%) were managed by an accident and emergency department. There was no change in the pattern of management relative to 1991/92. Compared with recommended guidelines there was underuse of systemic steroids and nebulised bronchodilators. Between 1991/92 and 1992/93 use of systemic steroids in acute attacks increased from 56% to 71%, nebulised bronchodilators from 31% to 32%, and an increase in prophylactic medication after an acute attack from 41% to 49%. Contrary to guidelines, antibiotic use increased from 32% to 40% of attacks. Practitioners from a special interest asthma group gave more of their patients systemic steroids and nebulised bronchodilators both in 1991/92 and 1992/93. CONCLUSIONS: Some aspects of the management of asthma attacks by general practitioners has changed in line with guidelines, but there is still a large gap between actual and recommended management.

BACKGROUND: As more developing countries adopt a westernised style of living, an increase in the prevalence of asthma can be expected to occur in these areas. A study was undertaken to establish the normal response to exercise in Ghanaian children and to use these normal values to determine the prevalence of exercise induced bronchospasm (EIB) in urban rich (UR), urban poor (UP), and rural (R) school children. Skin test reactivity to common inhalant allergens in UR, UP, and R children with and without EIB was also investigated. METHODS: Two hundred children aged 9-16 years without a previous history of respiratory symptoms were randomly selected and underwent free running exercise testing. A normal response to exercise was defined as the group mean change in peak expiratory flow rate (PEFR) +/- 2 standard deviations. This value was used to identify the prevalence of EIB in UR, UP, and R schoolchildren. A total of 1095 children from three different schools underwent exercise testing (220 UP, 599 UR, 276 R), after which 916 children underwent skin prick testing to six common inhalant allergens (D farinae, D pteronyssinus, cat, dog, Aspergillus flavus and Candida albicans). RESULTS: From the results of exercise testing in asymptomatic children the normal range was defined as a fall in PEFR of < 12.5% after exercise. Thirty four children were classified as having EIB on the basis of the above definition, giving an overall prevalence of 3.1%. The prevalence of EIB was significantly higher in UR children (4.7%) than in both UP (2.2%; p < 0.05) and R children (1.4%; p < 0.01). However, the prevalence rates in the UP and R children were similar. The prevalence of atopy in the whole population was 4.4%. Of the children with EIB, 10% were skin test positive to at least one of the allergens tested. The prevalence of atopy was significantly higher in UR children (6.55%, 95% confidence interval (CI) 4.5% to 9.2%) than in UP (2.9%, 95% CI 0.9% to 6.7%) and R children (1.5%, 95% CI 0.4% to 3.7%), respectively (p < 0.005). CONCLUSIONS: The prevalence of EIB and atopy is higher in urban rich than in urban poor or rural children suggesting that, in addition to genetic predisposition, social and environmental factors such as wealth, life style, and housing are important determinants of these phenotypes.

BACKGROUND: Intensive endurance training has been associated with a high prevalence of symptoms compatible with asthma in elite athletes. It is not known, however, whether there is an association between the type of training for competitive events and the risk of asthma in highly trained athletes. METHODS: Two hundred and thirteen track and field athletes, mostly from Finnish national teams, and 124 controls of the same age completed a respiratory symptom questionnaire. Positive answers to physician diagnosed asthma were confirmed by personal interviews. The athletes were divided into two groups depending on whether they were speed and power athletes (n = 106) or long distance runners (n = 107). RESULTS: According to a logistic regression model the prevalence of physician diagnosed asthma was not associated with age, sex, or a family history of asthma. Long distance runners (OR 6.7; 95% CI 2.1 to 22.1) and speed and power athletes (OR 3.2; 95% CI 0.90 to 11.4) had a higher prevalence of physician diagnosed asthma than control subjects. Physician diagnosed asthma was found in 18 of 107 long distance runners (17%), in nine of 106 speed and power athletes (8%; p = 0.07 (chi 2 test)), and in four of 124 controls (3%; p < 0.0004 (chi 2 test for trend)). CONCLUSIONS: The prevalence of physician diagnosed asthma is high in elite athletes and an association with the competitive event is suggested with long distance runners having a greater risk of developing asthma than speed and power athletes. This may be due to prolonged hyperventilation and increased exposure to inhalant allergens and irritants during endurance training and competition.

BACKGROUND: Rates of fresh gas flow (FGF) commonly used when continuous positive airway pressure (CPAP) is delivered by face mask theoretically reduce the delivery and availability of therapeutic aerosols. As it may be hazardous for patients with acute respiratory failure to interrupt mask CPAP, the effects of CPAP on aerosol kinetics and bronchodilator efficacy were investigated. METHOD: The effect of CPAP at 10 cm H2O at a FGF rate of 50 l/min on the delivery of technetium labelled aerosol generated from a readily available jet nebuliser was measured using a bench model of spontaneous respiration. In a separate clinical study the bronchodilator responses to incremental doses of nebulised salbutamol were measured in nine stable asthmatic subjects in a random sequence of conventional nebulisation (control) or nebulisation whilst receiving CPAP via a tight fitting face mask. Each patient acted as his or her own control. RESULTS: CPAP significantly reduced total aerosol delivery to the face mask from 6.85 (1.52)% to 1.3 (0.37)% of the initial nebuliser charge. In the clinical study a significant bronchodilator response to nebulised salbutamol was seen during both conventional nebulisation and nebulisation whilst receiving CPAP by face mask. The shape of the dose-response curves and the magnitude of the total increase in the forced expiratory volume in one second (FEV1) was identical for CPAP and control conditions. CONCLUSIONS: Despite a reduction in aerosol presented to the proximal airway, the bronchodilator response to inhaled beta 2 agonists in stable asthmatic subjects was not affected when CPAP was delivered by face mask. Despite a high rate of FGF, nebulised beta 2 agonists are effective when administered in conjunction with CPAP delivered by face mask.

BACKGROUND: Inhaled frusemide inhibits airway narrowing and causes a transient increase in forced expiratory volume in one second (FEV1) during hypertonic saline challenge. This inhibitory effect could be secondary to prostaglandin release during challenge. The involvement of prostaglandins in the inhibitory action of frusemide during challenge with 4.5% NaCl was investigated by premedicating with indomethacin, a prostaglandin synthetase inhibitor. METHODS: Fourteen asthmatic subjects (eight women) aged 26.6 (range 18-56) years participated in a double blind, placebo controlled, crossover study. The subjects attended five times and inhaled 4.5% NaCl for 0.5, 0.75, 1, 1.5, 2, 4, 8, 8, and 8 minutes, or part thereof, or until a provocative dose causing a 20% fall in FEV1 (PD20 FEV1) was recorded. Indomethacin (100 mg/day) or placebo were taken three days before all visits, except control day. The FEV1 was measured and frusemide (38.0 (6.4) mg, pH = 9) or vehicle (0.9% NaCl, pH = 9) were inhaled 10 minutes before the challenge. Bronchodilation was calculated as the percentage rise in FEV1 from the prechallenge FEV1 to the highest FEV1 recorded during the challenge. RESULTS: Frusemide caused a fold increase in PD20 FEV1 compared with the vehicle which was similar in the presence of both indomethacin and placebo (3.7 (95% CI 2.0 to 7.3) versus 3.3 (2.0 to 5.4)). Frusemide, but not vehicle, also caused a transient percentage rise in FEV1 during challenge with 4.5% NaCl which was not blocked by indomethacin (3.6% (1.2 to 6.0)) or placebo (3.1% (1.0 to 5.2)). CONCLUSIONS: Inhaled frusemide inhibited airway narrowing and caused a transient increase in FEV1 during challenge with 4.5% NaCl. These effects were not blocked by indomethacin, which suggests that the inhibitory action of frusemide is not secondary to prostaglandin release.

Peak flow monitoring is widely recommended in international asthma guidelines. However, suspicions about the accuracy of conventional pen and paper records were confirmed when studies with electronic spirometers showed poor adherence and falsification of data.1 There seems to be a prevailing nihilistic attitude to peak flow monitoring, largely based on the perception that satisfactory adherence cannot be achieved. We aimed to measure long term adherence to electronic peak flow monitoring when participants were aware that data were being stored and used to guide treatment. We obtained data from a 72 week randomised study comparing two starting doses of budesonide in patients aged 18-75 with poorly controlled asthma. The design and outcomes of the study are reported elsewhere.2 The study incorporated two novel features: twice daily monitoring with electronic diary spirometers (MicroMedical DiaryCard; MicroMedical, Rochester, UK) and titration of dose of budesonide (weeks 17-72) by using a clinical algorithm based on peak flow and diary data. …

Aims-To investigate the ability of circulating human IgG autoanti-IgE antibodies from asthma patients to block the binding of IgE to the alpha chain of the high affinity receptor (FcepsilonRI).Methods-This involved the use of a well validated flow cytometric method to detect inhibition of FITC labelled IgE binding to a fibroblast cell line (CHK1E1) transfected with the alpha chain of FcepsilonRI.Results-IgG autoanti-IgE-containing sera blocked the binding of IgE-FITC to the CHK1E1 cells. No such inhibition was demonstrable with rheumatoid sera containing autoanti-IgG (that is, rheumatoid factor) but lacking autoanti-IgE. Percentage inhibition (up to 50%) of IgE binding to the CHK1E1 cells was directly related to the titre of IgG1, but not IgG4, autoanti-IgE in the sera tested (correlation coefficient 0.66, probability 0.003).Conclusions-The capacity of anti-IgE to block the binding of IgE to FcepsilonRI has important clinical implications, particularly in terms of downregulation of allergic reactions.

Background: Few studies have used time series to investigate the relationship between asthma attacks and aeroallergen levels on a daily basis. Methods: This study, based on time series analysis adjusting for meteorological factors and air pollution variables, assessed the short term effects of different types of allergenic pollen on asthma hospital emergencies in the metropolitan area of Madrid (Spain) for the period 1995–8. Results: Statistically significant associations were found for Poaceae pollen (lag of 3 days) and Plantago pollen (lag of 2 days), representing an increase in the range between the 99th and 95th percentiles of 17.1% (95% confidence interval (CI) 3.2 to 32.8) and 15.9% (95% CI 6.5 to 26.2) for Poaceae and Plantago , respectively. A positive association was also observed for Urticaceae (lag of 1 day) with an 8.4% increase (95% CI 2.8 to 14.4). Conclusions: There is an association between pollen levels and asthma related emergencies, independent of the effect of air pollutants. The marked relationship observed for Poaceae and Plantago pollens suggests their implication in the epidemic distribution of asthma during the period coinciding with their abrupt release into the environment.