Allergic diseases are rare in areas with high helminth parasite exposure and common where helminth exposure is lacking or significantly reduced, such as urban areas of developing countries and industrialized nations. Studies suggest that helminths induce a systemic immuno-modulatory network, including regulatory T cells and anti-inflammatory IL-10, which might play a key role in the protection against the allergic phenotype. Here, we review the current cross-sectional, birth cohort, and intervention study evidence for a protective effect of helminth infection on allergy. There is increasing evidence for a causal relationship between helminth infection and reduced skin prick test responsiveness to allergens. Cross-sectional studies have shown a consistent negative relationship, and these results have been confirmed in several, although not all, intervention studies. The immunological basis for this protective effect is less clear. Recent studies do not support the mast-cell IgE saturation hypothesis, but suggest that protection is associated with IL-10 production. As for allergic disease, cross-sectional studies support a negative relationship between clinical asthma and infection with some helminth species, particularly hookworm, but more studies are required to draw conclusions for eczema and rhinitis. In addition, none of the few intervention studies to date have demonstrated an increase in clinical allergy after helminth treatment, and further studies are needed. Furthermore, we are only beginning to understand the host genetic factors that are potentially involved. A genetically predetermined T-helper type 2 cell-dominated cytokine milieu reduces parasite burden and may enhance host survival in an environment where helminth parasites are prevalent. Lack of parasite exposure in such hosts might lead to hypersensitivity to seemingly minor environmental allergen stimuli. Large birth cohort studies in helminth-endemic areas that use epidemiological, genetic, and immunological tools are required to further examine how helminth parasites affect the development of atopy and allergic disease. Intervention studies with hookworm in parasite-naïve allergic individuals are currently ongoing in the United Kingdom to test the above hypotheses further.

Asthma is one of the commonest chronic diseases of affluent societies. The striking increase in prevalence of asthma over recent decades and the rarity of this disease in less affluent populations confirms the importance of environmental factors in the cause of asthma--although which environmental factors are responsible is still not clear. Family studies show that genetic factors are also important in determining individual susceptibility to asthma, with results of genetic studies suggesting that there are many genes with moderate effects rather than a few major genes. Asthmatic airways show inflammation and remodelling, with CD4+ helper cells, mast cells, and eosinophils characterising the inflammatory response. Inhaled corticosteroids remain the cornerstone of treatment with the addition of long-acting beta agonists as the next step if symptoms continue. Leukotriene antagonists, the only new drugs to reach the market in the past decade, have modest effects. However, a better understanding of the mechanisms underlying asthma and the genetic and environmental factors that predispose individuals to asthma should lead to better preventative strategies and new therapeutic approaches.

Background -Pulmonary lymphangioleiomyomatosis is a rare progressive disease ofunknown aetiology affecting premenopausal women. Since the oral contraceptive pill has been implicated in its pathogenesis, a case control study was carried out to determine whether women with the disease were more likely to have taken the oral contraceptive pill, and whether the disease was associated with other conditions related to sex hormones including pregnancy, parity, and fibroids. Methods -All chest physicians in the UK were asked for details of all live patients with pulmonary lymphangioleiomyomatosis; the patient's family doctor was then asked for four age and sex matched control subjects from their patient register. Details of lifetime use of the oral contraceptive pill, pregnancy, parity, history of fibroids, and smoking were obtained from cases and controls. Relative odds of exposure to potential risk factors were estimated by conditional logistic regression. Results The aetiology of pulmonary lymphangioleiomyomatosis is unknown, but sex hormones have been assumed to be important since the disease develops exclusively in women and almost invariably women of reproductive age.'3"6 Treatment has usually invoved antioestrogen measures in the form of oophorectomy347 or treatment with tamoxifen,8-'0 medroxyprogesterone,8 '-and luteinising hormone releasing hormone analogues. 14 None of these treatments has been assessed in a controlled trial and their value is uncertain. 5 Reports of the disease occurring in women on the oral contraceptive pill2 16 -18 and of exacerbations of the disease during pregnancy8 have added to the suspicion that sex hormones are involved. We have therefore conducted a case control study to determine whether pulmonary lymphangioleiomyomatosis is associated with the use of the oral contraceptive pill or other conditions associated with sex hormones such as pregnancy, parity, and fibroids. Methods CASES AND CONTROLSChest physicians in the UK on the British Thoracic Society register were sent an explanation of the study and asked for details of all known live patients with pulmonary lymphangioleiomyomatosis. The physicians were asked to forward to such patients a written request asking them to participate in the study, plus a questionnaire and consent form which

Airway reactivity is known to increase in relation to the severity of asthma, and, in the community, hyperreactivity has been shown to be associated with respiratory symptoms such as wheezing and shortness of breath. However, the relation between change in airway reactivity and change in the severity of respiratory symptoms and change in the use of asthma medications within subjects has not been studied. We have investigated this relationship in a community population. In September 1984 and March 1985, the provocative dose of histamine producing a 20% fall in FEV1 (PD20) was measured, and respiratory symptoms and medication use assessed by questionnaire in 78 subjects taking part in a study of seasonal changes in airway reactivity. On both occasions, PD20 was negatively correlated with current frequency of wheezing, with the amount of asthma medication in regular use, and with the current general assessment of breathing problems. In the 45 subjects who had a PD20 value of 8 mumol or less on at least one of the two occasions tested, PD20 increased between September and March by 0.46 (SEM, 0.32) doubling doses of histamine (p = 0.16). Within subjects, change in PD20 was negatively correlated with change in the frequency of wheezing in the past month (p less than 0.005) and with change in medication use (p less than 0.05). This study demonstrates that PD20 is related to the severity of respiratory symptoms and medication use, and that change in airway reactivity within subjects in a community population is associated with changes in the frequency of wheezing and in the use of asthma medication.

Respiratory failure is an important terminal event in muscular dystrophy, but increasingly is effectively treated by non-invasive ventilation. This study was designed to assess mortality statistics in this patient group in order to get an indication of future demand. Mortality data for all deaths from muscular dystrophy registered by death certification in England and Wales between 1993 and 1999 were analysed. In total, 817 deaths from muscular dystrophy were registered between 1993 and 1999. Annual number of deaths was unchanged over this period. Median age at death (interquartile range) for all cause muscular dystrophy increased from 20 (17-42.5) years in 1993, to 26 (17.5-63) years in 1999. Respiratory failure was the primary or contributory cause of death in 82% of cases. Two thirds of these deaths were during acute infection. We can expect 100 patients with muscular dystrophy to develop respiratory failure in England and Wales each year, so non-invasive ventilation services probably need to be able to provide for 0.2 new patients per 100,000 population annually. Respiratory services also need to provide adequate monitoring and early treatment of infection in these patients.

To determine whether asthma mortality is influenced by geographical or social factors, a retrospective analysis of deaths from asthma in England and Wales between 1979-1987 was performed. Death rates in the 15 Regional Health Authority areas of England and Wales were stratified by sex, age group (0-4, 5-34, 35-64, and > 64 years), and occupational social class. Detailed analysis was restricted to subjects aged 5-64 years because adequate social class data was only available over this age range. Death rates were higher in manual occupational groups (social class IIIb-V) than in non-manual occupations (social class I-IIIa), but on further analysis this effect was confined to males aged 35-64 years. In younger subjects (5-34 years), mortality was higher in the south of the country, and this difference was significant in males (P < 0.05). In older subjects (35-64 years), mortality in both sexes was significantly higher in the north of the country. This study demonstrates that mortality is not evenly distributed between social classes or regions of the country.

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