Infections presenting for clinical care in early life and later risk of hay fever in two UK birth cohorts.

BACKGROUND: The 'hygiene hypothesis' proposes that infections in infancy protect against hay fever (HF). We investigated infections during infancy in relation to HF, including rarer ones not previously researched in this context, while examining the role of potential confounding variables. METHODS: From birth cohorts derived within the General Practice Research Database (GPRD) and Doctors Independent Network (DIN) database of computerized patient records from UK general practice, we selected 3549 case-control pairs, matched for practice, age, sex and control follow-up to case diagnosis. Conditional logistic regressions were fitted for each of 30 infections; behavioural problems (BP) acted as a control condition unrelated to HF. Odds ratios (OR), adjusted for consultation frequency were pooled across the databases using fixed effect models. We also adjusted for sibship size in GPRD and a socioeconomic marker in DIN. RESULTS: Upper respiratory tract infections, diarrhoea and vomiting and acute otitis media in infancy were each related with a moderately increased risk of HF in both databases, as were BP. These associations were lost on adjustment for consultation frequency. Only bronchiolitis was significantly associated with a reduced pooled risk of HF after adjustment for consultations (OR = 0.8). Adjustment for sibship size in GPRD and a socioeconomic marker in DIN had little impact on the OR. CONCLUSIONS: Of 30 infectious illnesses investigated, none had strong or consistent associations with HF after adjustment for consultation frequency. Except for bronchiolitis, possibly a chance finding, none of the clinically apparent infections considered appear to have an important role in allergy prevention.

Vaccinations, infections and antibacterials in the first grass pollen season of life and risk of later hayfever.

BACKGROUND: It has been hypothesized that early-life exposure to vaccinations, infections or antibacterials influence allergic disease development. Concurrent exposure to grass pollens may alter any effect. OBJECTIVE: To test the hypothesis that exposure to antibacterials, vaccinations (DTP or MMR) or specific infections during the first grass pollen seasons of life influences the risk of hayfever more than at any other time of the year. METHODS: Nested case-control studies were based on birth cohorts within two large databases of computerized patient records from UK general practices: the General Practice Research Database (GPRD) and Doctors' Independent Network (DIN). Seven thousand ninety-eight hayfever cases, diagnosed after age 2, were matched to controls for practice, age, sex and follow-up of control to case ascertainment date. Conditional logistic regression was used to compare exposure by age 1 (age 2 for MMR) inside vs. outside the grass pollen season (May, June, July). Odds ratios (ORs) were pooled across databases. RESULTS: There were no associations in either database between MMR during vs. outside the grass pollen season and later hayfever. Of 23 infections studied, none were statistically significant; although analyses for the less common conditions were limited by low statistical power. The pooled OR for hayfever comparing exposure to antibacterials only in the grass pollen season with only outside it was 1.20 (95% CI 0.98-1.47) and for DTP was 0.84 (95% CI 0.72-0.98). CONCLUSION: Although an interaction between early exposure to microbial agents and concurrent grass pollen exposure on hayfever risk seemed plausible, there was little evidence to support it across a range of analyses. However, the effect of DTP though weak deserves further study.

Timing of routine immunisations and subsequent hay fever risk.

BACKGROUND: Suggestions that immunisation influences allergic disease risk, either positively (pertussis) or negatively (BCG) are of concern for vaccination policy. AIMS: To determine whether DTP, MMR, and BCG vaccination in infancy influenced hay fever risk. METHODS: Case-control study of 7098 hay fever cases and controls, within two primary care databases. One control per case was matched for practice, age, and sex. Odds ratios (OR) were derived using conditional logistic regression. RESULTS: Compared to those completing in month 5 (base group) (39.3%), DTP unvaccinated children (4.3%) had a similar risk of hay fever (OR = 0.94, 95% CI 0.73 to 1.23). However, those completing after 12 months (4.2%) had a reduced risk (OR = 0.60, 95% CI 0.45 to 0.76) compared to the base group. Compared to those vaccinated in month 14 (base group) (29.5%), MMR unvaccinated children (2.3%) had an OR of 0.79 (95% CI 0.58 to 1.08). Completion of MMR after two years was associated with reduced hay fever risk (OR = 0.62, 95% CI 0.48 to 0.80) compared to the base group. The effects of late immunisation with DTP and MMR were independent. Those vaccinated with BCG by age 2 (2.4%) had an odds ratio of 1.28 (95% CI 0.96 to 1.70). Adjustment for consulting behaviour, social factors, or sibship size did not alter these associations. CONCLUSIONS: Immunisation against DTP or MMR does not increase the risk of hay fever. The lower confidence limit for BCG vaccination contradicts the hypothesised protective effect. The reduced risk of hay fever among children immunised late may be explained by a third factor causing both postponement and reduced risk such as intercurrent febrile illnesses.

Early-life exposure to antibacterials and the subsequent development of hayfever in childhood in the UK: case-control studies using the General Practice Research Database and the Doctors' Independent Network.

BACKGROUND: Theoretically, antibacterial agents in early life might influence allergic sensitization in two ways: (i) as an indicator of infectious illness, they might be expected to protect against allergy; (ii) alternatively they might increase the risk through effects on the commensal bowel flora. Epidemiological evidence linking the prescription of antibacterial agents in early life to the subsequent development of hayfever is conflicting. OBJECTIVE: To establish definitively whether an association exists between early-life antibacterial exposure and childhood hayfever diagnosis. METHODS: Nested case-control studies were based on birth cohorts of children identified within two large UK general practice databases of electronic patient records. One hundred and sixteen thousand and four hundred and ninety-three children from 605 general practices were identified as being continuously registered from birth to at least age 5 years. Seven thousand and ninety-eight cases were diagnosed with hayfever after the age of 2 years. One control per case was matched for practice, birth month, sex and still being registered on case diagnosis date. Odds ratios were derived from conditional logistic regressions within each database followed by pooling using a fixed-effect model. RESULTS: The pooled odds ratio for hayfever was 1.11, 95% CI (1.03-1.20) if exposed to antibacterials in the first year of life, 1.35 (1.25-1.46) in year 2 and 1.47 (1.37-1.59) in year 3. Adjusting for consultation frequency reduced these odds ratios to 0.92, 1.05 and 1.10, respectively. There was no evidence that broader spectrum antibacterials, exposure in any specific month of year 1 or in the grass pollen season influenced the risk of hayfever. CONCLUSION: These data exclude any important effect of antibacterial exposure in infancy on subsequent hayfever risk. Associations reported in earlier studies have likely been exaggerated through publication bias and by lack of control for the tendency of some families to consult frequently for a range of conditions.

Increasing prevalence of asthma in UK primary care during the 1990s.

OBJECTIVE: To estimate recent prevalence trends of physician-diagnosed asthma in primary care in the UK, and to test the hypothesis that the asthma epidemic in the UK peaked in the mid-1990s and is currently declining. METHODS: A retrospective cohort of asthma patients was obtained from the General Practice Research Database (GPRD). From January 1990 to February 1999, asthmatics were followed up to death, censoring or mention of chronic obstructive pulmonary disease (COPD) in their clinical record. Prevalence rates of ever and managed asthma were obtained by sex, age and calendar year. RESULTS AND CONCLUSION: From 1990 to 1998, annual prevalence rates of managed physician-diagnosed asthma in women rose from 3.01% (95%CI 2.99-3.03) to 5.14% (95%CI 5.10-5.18), and in men from 3.44% (95%CI 3.41-3.46) to 5.06% (95 %CI 5.02-5.10) (P for trend <0.01 in both). In 1998, prevalence rates of managed asthma in children aged 5-14 affected 7.86% (95%CI 7.71-8.00) of girls and 10.30% (95%CI 10.15-10.47) of boys. Increasing prevalence rates in adult asthma (maximum 4.11% in 1998, 95%CI 4.03-4.19) and elderly asthma (maximum 3.37% in 1998, 95%CI 3.29-3.46) were observed as well in 1998. The study shows that the burden of asthma in UK primary care during the 1990s was still increasing.

Prospective observational cohort safety study to monitor the introduction of a non-CFC formulation of salbutamol with HFA134a in England.

OBJECTIVE: To monitor the safety of a salbutamol MDI with a hydrofluoroalkane propellant (Ventolin Evohaler) during its introduction into primary care use in England. METHODS: Prospective observational cohort study. 1,365 GPs in England submitted data on 10,472 regular users of Ventolin MDI, over five 3-month periods of observation between October 1, 1998 and December 31, 1999. The primary aim was to compare event rates occurring before and after the introduction of Ventolin Evohaler. The secondary aim was a comparison of event rates between users of Ventolin Evohaler and Ventolin MDI. The main outcome measures were: indication for use of Ventolin MDI, assessment of disease severity, event rates during each period of observation; deaths, pregnancies, reported adverse drug reactions and reasons for discontinuation of MDI. Event rates were adjusted using a ratio for under-reporting derived from a validation study on 4.6% of the study population and stratified by severity of indication. RESULTS: The primary indication was asthma in 94%, distributed by severity as 47% mild, 44% moderate and 9% severe; 13% were children. By October 1999, 52.7% of the 8,973 remaining patients had transitioned to Ventolin Evohaler. There was no increase in major or minor events observed following the introduction of Ventolin Evohaler. No serious adverse events, abnormal pregnancy outcomes or deaths have been related to Ventolin MDI or Ventolin Evohaler. The validation study showed a degree of under-reporting. CONCLUSION: These results on a large cohort of community patients in England indicate that Ventolin Evohaler is well tolerated among asthmatics.

Survival in COPD patients after regular use of fluticasone propionate and salmeterol in general practice.

Despite substantial evidence regarding the benefits of combined use of inhaled corticosteroids and long-acting beta2-agonists in asthma, such evidence remains limited for chronic obstructive pulmonary disease (COPD). Observational data may provide an insight into the expected survival in clinical trials of fluticasone propionate (FP) and salmeterol in COPD. Newly physician-diagnosed COPD patients identified in primary care during 1990-1999 aged > or = 50 yrs, of both sexes and with regular prescriptions of respiratory drugs were identified in the UK General Practice Research Database. Three-year survival in 1,045 COPD patients treated with FP and salmeterol was compared with that in 3,620 COPD patients who regularly used other bronchodilators but not inhaled corticosteroids or long-acting beta2-agonists. Standard methods of survival analysis were used, including adjustment for possible confounders. Survival at year 3 was significantly greater in FP and/or salmeterol users (78.6%) than in the reference group (63.6%). After adjusting for confounders, the survival advantage observed was highest in combined users of FP and salmeterol (hazard ratio (HR) 0.48 (95% confidence interval 0.31-0.73)), followed by users of FP alone (HR 0.62 (0.45-0.85)) and regular users of salmeterol alone (HR 0.79 (0.58-1.07)) versus the reference group. Mortality decreased with increasing number of prescriptions of FP and/or salmeterol. In conclusion, regular use of fluticasone propionate alone or in combination with salmeterol is associated with increased survival of chronic obstructive pulmonary disease patients managed in primary care.

Asthma control and differences in management practices across seven European countries.

Failure to follow asthma management guidelines may result in poor asthma control for many patients. The Asthma Insights and Reality in Europe (AIRE) survey, a multi-national survey assessing the level of asthma control from the patients perspective in seven Western European countries, previously demonstrated that the Global Initiative for Asthma (GINA) guideline goals were not achieved in Western Europe and that both adults and children with asthma were poorly controlled. Using additional data on asthma management practices from each of the seven countries in the AIRE survey, we compared variations in asthma morbidity and asthma management practices across countries to provide insight into the reasons for poor asthma control. Asthma management practices and asthma control among adults and children with current asthma were suboptimal in each of seven countries surveyed. Among patients with symptoms of severe persistent asthma, over 40% reported their asthma was well or completely controlled. School absence due to asthma was reported by upto 52.7% of children and up to 27.6% of adult reported work absence due to asthma. Lung function testing in the past year was uncommon: ranging from 13.5% of children in the U.K. to 68.8% of adults in Germany. Written asthma management plans were used by less than 50% of adults and less than 61% of children in all seven countries. Most adults (49.5-73.0%) and a large proportion of children (38.4-70.6%) had follow-up visits for their asthma only when problems developed. The ratio of recent inhaled corticosteroid use to recent short-acting beta-agonist use was inappropriate (<1) among patients with symptoms of severe asthma in all countries. This disparity was greatest among adults in Italy and France, where recent inhaled corticosteroid use was reported by less than one in nine patients reporting recent use of short-acting bronchodialators (IS:SAB <0.11). Management practices differ between countries and additional public health interventions and resources may be necessary to reduce patient suffering. Further efforts to fully implement asthma management guidelines are required to improve asthma control in Europe.

The risk of cataract among users of inhaled steroids.

Prolonged exposure to inhaled corticosteroids among adults over 49 years old has been reported to increase cataract risk. Small-scale studies of inhaled steroid users suggest that no increased risk for children and young adults exists. To describe cataract risk among people with asthma who use inhaled corticosteroids relative to patients with asthma with no history of corticosteroid use, we conducted a retrospective observational cohort study of patients identified from the United Kingdom-based General Practice Database with a nested case-control analysis. Relative to patients who do not use corticosteroids, all inhaled corticosteroid users were at a marginally increased risk of cataract (RR = 1.3). Among individuals 40 years of age or older, the risk ratio increased with use of increasing numbers of inhaled corticosteroid prescriptions after controlling for diabetes mellitus, hypertension, and smoking history. This trend was not evident in those under age 40.

Validation of general practitioner-diagnosed COPD in the UK General Practice Research Database.

BACKGROUND: Information in large, automated databases can be useful to study the natural history of respiratory diseases in the community, but the validity of definitions needs to be demonstrated. AIM: To compare a simple computer algorithm that identifies patients diagnosed with chronic obstructive pulmonary disease (COPD) and severity of COPD in the UK General Practice Research Database (GPRD) with general practitioner (GP) clinical records, to evaluate the utility of this algorithm for identifying COPD patients and for distinguishing COPD from asthma. METHODS: Using a computer algorithm identifying patients by diagnostic codes and allotting three grades of severity by drug use, a sample of 225 patients in the GPRD with a diagnosis of COPD and an age-sex matched group of 75 patients with asthma were randomly selected. Questionnaires were posted to the GPs of the 300 selected patients who were asked to state diagnosis and to grade severity based on the individual's medical record. Agreement was quantified with the kappa index, an estimator that accounts for agreement that occurs by chance. RESULTS: Response rate was 85.7%. The concordance between COPD diagnosis by the GPRD algorithm with that of the GP was quantified as a kappa of 0.52, and the concordance between COPD severity by the GPRD algorithm with that of the GP was quantified as a kappa of 0.54. The kappa index for COPD diagnosis increased with increasing severity of COPD (0.46, 0.59, and 0.68 for mild, moderate and severe COPD, respectively), but similar good agreement was observed in a stratified analysis by sex, age, smoking status and number of comorbidities. CONCLUSIONS: It is concluded that the GPRD algorithms used for diagnosis and severity of COPD are a good screening tool for COPD in the UK general population, and satisfactorily differentiate COPD from asthma patients, particularly when disease is moderate or severe.

Recent trends in physician diagnosed COPD in women and men in the UK.

BACKGROUND: Recent trends in physician diagnosed chronic obstructive pulmonary disease (COPD) in the UK were estimated, with a particular focus on women. METHODS: A retrospective cohort of British patients with COPD was constructed from the General Practice Research Database (GPRD), a large automated database of UK general practice data. Prevalence and all-cause mortality rates by sex, calendar year, and severity of COPD, based on treatment only, were estimated from January 1990 to December 1997. RESULTS: A total of 50 714 incident COPD patients were studied, 23 277 (45.9%) of whom were women. From 1990 to 1997 the annual prevalence rates of physician diagnosed COPD in women rose continuously from 0.80% (95% CI 0.75 to 0.83) to 1.36% (95% CI 1.34 to 1.39), (p for trend <0.01), rising to the rate observed in men in 1990. Increases in the prevalence of COPD were observed in women of all ages; in contrast, a plateau was observed in the prevalence of COPD in men from the mid 1990s. All-cause mortality rates were higher in men than in women (106.8 versus 82.2 per 1000 person-years), with a consistently increased relative risk in men of 1.3 even after controlling for the severity of COPD. Significantly increased mortality rates were also observed in adults aged less than 65 years. The mean age at death was 76.5 years; patients with severe COPD died an average of three years before those with mild disease (p<0.01) and four years before the age and sex matched reference population. CONCLUSIONS: While prevalence rates of COPD in the UK seem to have peaked in men, they are continuing to rise in women. This trend, together with the ageing of the population and the long term cumulative effect of pack-years of smoking in women, is likely to increase the present burden of COPD in the UK.

Risk of cataract among users of intranasal corticosteroids.

BACKGROUND: Oral corticosteroid users are at increased risk of cataract, but the risk among intranasal corticosteroids users is unknown. OBJECTIVE: Our purpose was to describe the risk of cataract among users of intranasal steroids. METHODS: A retrospective observational cohort study of cataract incidence was conducted among users of oral and intranasal steroids identified from the United Kingdom-based General Practice Research Database with a nested case-control analysis to control for confounding factors. The study population included 286,078 subjects aged less than 70 years old drawn from 350 general practices in England and Wales. Patients were classified as users of only intranasal corticosteroids, users of only oral corticosteroids, and nonusers of either medication. Computerized medical records were used to identify cases of cataract. Two hundred twenty-five cases were randomly selected for validation against general practitioners' held referral and hospitalization letters. RESULTS: The incidence rate of cataract (1.0/1000 person-years) among users of intranasal corticosteroids was similar to the incidence rate among nonusers. However, oral corticosteroid users were at higher risk of cataract (2.2/1000 person-years). Approximately 70% of intranasal corticosteroid exposure was to beclomethasone dipropionate only; the event rate in this group was similar to that in the unexposed group. Cataract risk did not increase with the number of prior prescriptions for intranasal corticosteroids. CONCLUSION: The use of intranasal corticosteroids was not associated with an increased risk of cataracts in this study population.

Clinical management of asthma in 1999: the Asthma Insights and Reality in Europe (AIRE) study.

Asthma management guidelines provide recommendations for the optimum control of asthma. This survey assessed the current levels of asthma control as reported by patients, which partly reflect the extent to which guideline recommendations are implemented. Current asthma patients were identified by telephone by screening 73,880 households in seven European countries. Designated respondents were interviewed on healthcare utilization, symptom severity, activity limitations and asthma control. Current asthma patients were identified in 3,488 households, and 2,803 patients (80.4%) completed the survey. Forty-six per cent of patients reported daytime symptoms and 30% reported asthma-related sleep disturbances, at least once a week. In the past 12 months, 25% of patients reported an unscheduled urgent care visit, 10% reported one or more emergency room visits and 7% reported overnight hospitalization due to asthma. In the past 4 weeks, more patients had used prescription quick-relief medication (63%) than inhaled corticosteroids (23%). Patient perception of asthma control did not match their symptom severity; approximately 50% of patients reporting severe persistent symptoms also considered their asthma to be completely or well controlled. The current level of asthma control in Europe falls far short of the goals for long-term asthma management. Patients' perception of asthma control is different from their actual asthma control.

The impact of asthma and asthma-like illness in Seattle school children.

The impact of asthma and asthma-like illness was measured in a population of 5-9-year-old Seattle public school children. Child health information was obtained from a survey of 1665 parents of first and second grade students to assess medical services use and impaired physical functioning among diagnosed asthmatics and those with current wheezing, defined as wheezing in the past 12 months without a diagnosis of asthma, relative to an asymptomatic population with neither condition. Relative to the asymptomatic population, the prevalence of respiratory-related activity limitation, and perception of poorer child health was larger among diagnosed asthmatics than children with current wheezing. However, the prevalence of sleep disturbances, school absences, medical services use, and parental concern over their child's health was similar for both the asthmatic and wheezing groups relative to the asymptomatic group. Also, in both symptomatic groups, a history of moderate or severe wheezing was associated with an increased prevalence of respiratory-related sleep disturbances and activity limitation. The similarity between the impact of diagnosed asthma and undiagnosed asthma-like illness suggests that the overall social and economic burden of asthma may be higher than previously estimated.

Indoor risk factors for asthma and wheezing among Seattle school children.

Indoor risk factors for physician-diagnosed asthma and wheezing in the past 12 months without previous asthma diagnosis were assessed in a survey of parents of 5-9-year-old Seattle primary school students. Among the 925 respondents, 106 (11%) reported a physician diagnosis of asthma, 66 (7%) had wheezing without diagnosis, and 753 (82%) were asymptomatic. After adjusting for age, sex, gender, ethnicity, medical history, socioeconomic status (SES) and parental asthma status, an increased risk of physician diagnosis of asthma was associated with household water damage, the presence of one or more household tobacco smokers, and at least occasional environmental tobacco smoke (ETS) exposure. Similarly, an increased risk of wheezing in the past 12 months among children without diagnosed asthma was associated with household water damage, presence of one or more household tobacco smokers, and occasional or more frequent ETS exposure. No increased risk of either condition was associated with gas, wood, or kerosene stove use, household mold, basement water, or wall/window dampness. Similarities in the indoor risk factors patterns between diagnosed asthma and wheezing without diagnosis suggested a similar etiology of these two conditions. The slightly higher association between ETS and asthma may indicate that parents of diagnosed asthmatics were more conscious of ETS, and were more likely to prohibit household smoking by resident smokers. Future research is needed to quantify which aspects of household water damage are related to respiratory illness.

Differences between individuals with self-reported irritable bowel syndrome (IBS) and IBS-like symptoms.

Although there are several symptom classification systems for irritable bowel syndrome (IBS), for example, the Manning or Rome criteria, there has been no previous research on how well these classifications correspond to each other or to persons diagnosed with IBS. We examined data from the Digestive Disorders Supplement of the 1989 National Health Interview Survey (NHIS) to assess demographic, socioeconomic, and health status characteristics of two groups of IBS sufferers--those who met the Manning or Rome criteria and those who reported having IBS but did not meet either criteria. The results showed that the overlap between estimates of IBS and persons with IBS-like symptoms depended on the definition of IBS. There were socioeconomic differences between the two IBS groups and higher rates of functional or work-related activity limitation and health care utilization for all IBS groups relative to US national averages. In summary, these findings indicate that IBS affects a large portion of the US population, regardless of the definition used to describe the condition. Our results suggest that there is a large undiagnosed population with numerous symptoms consistent with IBS, but further research is required to determine the differences between people who do and do not seek care, their impact on the health care system, and future therapies to reduce symptomatology and suffering.