Decreased FEV1 % in asthmatic adults in Scottish homes with high Environmental Relative Moldiness Index values.

BACKGROUND: Exposures to indoor biological contaminants have been implicated in asthma's aetiology but their effect on lung function is not well quantified. OBJECTIVE: The aim of this cross-sectional study of non-smoking, asthmatic adults in Scotland was to determine the correlation between the results from a standard spirometry test, forced expiratory volume in one-second percent (FEV1 %), and quantitative estimates of some biological exposures. METHODS: A population (n = 55) of non-smoking, adult asthmatics in Scotland was included in this study and each completed a questionnaire that allowed the determination of the Asthma Control Questionnaire scores (ACQ) and St. George's Respiratory Questionnaire scores (SGRQ), as well as corticosteroid use. Spirometry testing was completed and the pre-bronchodilator FEV1 % value calculated. At about the same time, floor dust samples were collected in the living room and in the bedroom. These dust samples were analysed for mould contamination, as described by the Environmental Relative Moldiness Index (ERMI) values and by (1, 3)-ß-D-glucan concentrations, for endotoxin, and for dust mite, cat, and dog allergen concentrations. The asthmatics' FEV1 % values were tested for correlation (Pearson) to questionnaire-based estimates of health. Also, each biological exposure was tested for correlation (Pearson) to the FEV1 % values. RESULTS: FEV1 % results were correlated with ACQ scores (ρ -0.586, P < 0.001), SGRQ scores (ρ -0.313, P = 0.020), and weakly with corticosteroid use (ρ -0.221, P = 0.105). The ERMI values in the homes (average 5.3) were significantly correlated with FEV1 % values (ρ -0.378, P = 0.004). There was no correlation between FEV1 % and concentrations of endotoxin, (1, 3)-ß-D-glucan, or any of the allergens. CONCLUSION AND CLINICAL RELEVANCE: Although these results do not prove that mould exposures caused the deficit in lung function observed in this study, it might be advisable for asthmatics to avoid high ERMI environments.

Arachidonic acid metabolites and enzyme transcripts in asthma are altered by cigarette smoking.

BACKGROUND: Arachidonic acid metabolites are implicated in the pathogenesis of asthma although only limited information is available on the impact of current smoking history on these metabolites. The aim of the study was to examine the effect of smoking status on urinary, sputum, and plasma eicosanoid concentrations and relevant enzyme transcripts in asthma. METHODS: In 108 smokers and never smokers with asthma and 45 healthy controls [smokers and never smokers], we measured urinary tetranor prostaglandin (PG)D2 (PGDM) and leukotriene (LT)E4 , induced sputum fluid LTB4 , LTE4 , PGD2 , and PGE2 , plasma secretory phospholipase A2 (sPLA2 ), and 11ß prostaglandin F2α (11ßPGF2α ), and, in a subgroup with severe asthma, airway leukocyte and epithelial cell mRNA expression levels of arachidonic acid metabolic enzymes. RESULTS: Smokers with asthma had higher urinary LTE4 ; 83 (59, 130) vs 59 (40, 90) pg/mg creatinine, P = 0.008, and PGDM; 60 (35, 100) vs 41 (28, 59) ng/mg creatinine, P = 0.012 concentrations, respectively, and lower sputum PGE2 concentrations 80 (46, 157) vs 192 (91, 301) pg/ml, P = 0.001 than never smokers with asthma. Sputum LTB4 (P = 0.013), and plasma 11ßPGF2α (P = 0.032), concentrations, respectively, were increased in smokers with asthma compared with healthy smokers. Asthma-specific and smoking-related increases (>1.5-fold expression) in arachidonate 15-lipoxygenase and gamma-glutamyltransferase transcripts were demonstrated. CONCLUSIONS: Several arachidonic acid metabolites and enzyme transcripts involving both lipoxygenase and cyclooxygenase pathways are increased in smokers with asthma and differ from never smokers with asthma. Possibly targeting specific lipoxygenase and cyclooxygenase pathways that are activated by asthma and cigarette smoking may optimize therapeutic responses.

Long-term macrolide treatment of chronic inflammatory airway diseases: risks, benefits and future developments.

Macrolide antibiotics were discovered over 50 years ago and following their use as antimicrobials it became apparent that this group of antibiotics also possessed anti-inflammatory properties. Subsequent clinical trials showed benefits of macrolides as long-term adjuncts in the treatment of a spectrum of chronic inflammatory respiratory diseases, particularly diffuse panbronchiolitis, cystic fibrosis, post-transplant bronchiolitis obliterans and more recently chronic obstructive pulmonary disease (COPD). The evidence for efficacy of macrolides in the long-term treatment of chronic asthma and bronchiectasis is less well established. The mechanism(s) of action of macrolides in the treatment of these diseases remains unexplained, but may be due to their antibacterial and/or anti-inflammatory actions, which include reductions in interleukin-8 production, neutrophil migration and/or function. Macrolides have additional potentially beneficial properties including anti-viral actions and an ability to restore corticosteroid sensitivity. The increased prescribing of macrolides for long-term treatment could result in the development of microbial resistance and adverse drug effects. New macrolides have been developed which do not possess any antimicrobial activity and hence lack the ability to produce microbial resistance, but which still retain immunomodulatory effects. Potentially novel macrolides may overcome a significant barrier to the use of this type of drug for the long-term treatment of chronic inflammatory airway diseases.

Interleukin-33 amplifies IgE synthesis and triggers mast cell degranulation via interleukin-4 in naïve mice.

BACKGROUND: The regulation and function of IgE in healthy individuals and in antigen-naïve animals is not well understood. IL-33 administration increases serum IgE in mice with unknown mechanism. We tested the hypothesis that IL-33 provides an antigen-independent stimulus for IgE production and mast cell degranulation. METHODS: IL-33 was administered to naïve wild-type (WT), nude and ST2(-/-) , IL-4(-/-) , IL4Rα(-/-) and T-or B-cell-specific IL-4Rα(-/-) mice. IgE and cytokines were quantified by ELISA. T- and B-lymphocyte numbers and CD40L expression were determined by flow cytometry. Anaphylaxis was measured by temperature, mast cell degranulation and histamine release. RESULTS: IL-33 enhanced IgE production in naïve WT, T-IL-4Rα(-/-) but not in ST2(-/-) , IL-4(-/-) , IL-4Rα(-/-) or B-cell-specific IL-4Rα(-/-) mice, demonstrating IL-33 specificity and IL-4 dependency. Moreover, IL-4 was required for IL-33-induced B-cell proliferation and T-cell CD40L expression, which promotes IgE production. IL-33-induced IL-4 production was mainly from innate cells including mast cells and eosinophils. IL-33 increased mast cell surface IgE and triggered degranulation and systemic anaphylaxis in allergen-naïve WT but not in IL-4Rα(-/-) mice. CONCLUSION: IL-33 amplifies IgE synthesis and triggers anaphylaxis in naïve mice via IL-4, independent of allergen. IL-33 may play an important role in nonatopic allergy and idiopathic anaphylaxis.

Peripheral blood dendritic cell subtypes are significantly elevated in subjects with asthma.

BACKGROUND: Dendritic cells (DCs) are crucial for the processing of antigens, T lymphocyte priming and the development of asthma and allergy. Smokers with asthma display altered therapeutic behaviour and a reduction in endobronchial DC CD83 expression compared with non-smokers with asthma. No information is available on the impact of smoking on peripheral blood DC profiles. OBJECTIVE: Determine peripheral blood DC profiles in subjects with and without asthma with differing smoking histories. METHODS: Forty-three asthmatics (17 smokers, nine ex-smokers and 17 never-smokers) and 16 healthy volunteers (nine smokers and seven never-smokers) were recruited. Spirometry, exhaled nitric oxide and venesection was performed. DC elution was by flow cytometry via the expression of DC surface markers [plasmacytoid (pDC) (BDCA-2, CD303), type 1 conventional (cDC) (BDCA-1, CD1c), and type 2 cDC (BDCA-3, CD141)]. RESULTS: Subjects with asthma displayed increases in all DC subtypes compared with normal never-smokers: [type 1 cDCs - asthma [median% (IQR)]: 0.59% (0.41, 0.74), normal never-smokers: 0.35% (0.26, 0.43), P=0.013]; type 2 cDCs - asthma: 0.04% (0.02, 0.06), normal never-smokers: 0.02% (0.01, 0.03), P=0.008 and pDCs - asthma: 0.32% (0.27, 0.46), normal never-smokers: 0.22% (0.17, 0.31), P=0.043, and increased pDC and type 1 cDCs compared with normal smokers. Smoking did not affect DC proportions in asthma. Cigarette smoking reduced pDC proportions in normal subjects [normal never-smokers: 0.22% (0.17, 0.31); normal smokers: 0.09% (0.08, 0.15), P=0.003]. CONCLUSIONS AND CLINICAL RELEVANCE: This study shows for the first time that subjects with asthma display a large increase in peripheral blood DC proportions. Cigarette smoking in asthma did not affect the peripheral blood DC profile but did suppress pDC proportions in non-asthmatic subjects. Asthma is associated with a significant increase in circulating DCs, reflecting increased endobronchial levels and the importance of DCs to the development and maintenance of asthma. (Clinical trials.gov identifier: NCT00411320)

Were monocytes responsible for initiating the cytokine storm in the TGN1412 clinical trial tragedy?

The precise biological mechanisms that caused the TGN1412 clinical trial tragedy (also known as 'The Elephant Man Clinical Trial') in March 2006 remain a mystery to this day. It is assumed widely that the drug used in this trial (TGN1412) bound to CD28 on T lymphocytes and following activation of these cells, a massive 'cytokine storm' ensued, leading ultimately to multi-organ failure in all recipients. The rapidity of this in vivo response (within 2 h), however, does not fit well with a classical T lymphocyte response, suggesting that other 'faster-acting' cell types may have been involved. In this study we have activated purified human peripheral blood leucocyte populations using various clones of mouse monoclonal anti-CD28 presented to cells in the form of a multimeric array. Cytokines were measured in cell-free supernatants at 2 h, and specific mRNA for tumour necrosis factor (TNF)-α, thought to be the initiator of the cytokine storm, was also measured in cell lysates by reverse transcription-polymerase chain reaction (RT-PCR). Monocytes were the only cell type found to show significant (P < 0·05) up-regulation of TNF-α at 2 h. Eleven other monocyte cytokines were also up-regulated by anti-CD28 within this time-frame. It therefore seems likely that monocytes and not T cells, as widely believed, were probably responsible, at least in part, for initiating the cytokine storm. Furthermore, we propose that a multimeric antibody array may have formed in vivo on the vascular endothelium via an interaction between TGN1412 and CD64 (FcγRI), and we provide some evidence in support of this hypothesis.

Effect of low-dose theophylline plus beclometasone on lung function in smokers with asthma: a pilot study.

Smoking is common in asthma and is associated with worse asthma control and a reduced therapeutic response to corticosteroids. The present authors hypothesised that treating smokers with asthma with low-dose theophylline added to inhaled corticosteroids would enhance steroid sensitivity and thereby improve lung function and symptoms. In a double-blind, parallel group exploratory trial, 68 asthmatic smokers were randomised to one of three treatments for 4 weeks: inhaled beclometasone (200 microg day(-1)), theophylline (400 mg day(-1)) or both treatments combined. Outcome measures included change in lung function and Asthma Control Questionnaire (ACQ) scores. At 4 weeks, theophylline added to inhaled beclometasone produced an improvement in peak expiratory flow (39.9 L min(-1), 95% confidence intervals (CI) 10.9-68.8) and ACQ score (-0.47, 95% CI -0.91- -0.04) and a borderline improvement in pre-bronchodilator forced expiratory volume in one second (mean difference 165 mL, 95% CI -13-342) relative to inhaled corticosteroid alone. Theophylline alone improved the ACQ score (-0.55, 95% CI -0.99- -0.11), but not lung function. In the present pilot study, the combination of low-dose theophylline and inhaled beclometasone produced improvements in both lung function and symptoms in a group of smokers with asthma. Larger trials are required to extend and confirm these findings.

Effect of improved home ventilation on asthma control and house dust mite allergen levels.

BACKGROUND: The warm, humid environment in modern homes favours the dust mite population, but the effect of improved home ventilation on asthma control has not been established. We tested the hypothesis that a domestic mechanical heat recovery ventilation system (MHRV), in addition to allergen avoidance measures, can improve asthma control by attenuating re-colonization rates. METHODS: We conducted a randomized double-blind placebo-controlled parallel group trial of the installation of MHRV activated in half the homes of 120 adults with asthma, allergic to Dermatophagoides pteronyssinus. All homes had carpets steam cleaned and new bedding and mattress covers at baseline. The primary outcome was morning peak expiratory flow (PEF) at 12 months. RESULTS: At 12 months, the primary end-point; change in mean morning PEF as compared with baseline, did not differ between the MHRV group and the control group (mean difference 13.5 l/min, 95% CI: -2.6 to 29.8, P = 0.10). However, a secondary end-point; evening mean PEF, was significantly improved in the MHRV group (mean difference 24.5 l/min, 95% CI: 8.9-40.1, P = 0.002). Indoor relative humidity was reduced in MHRV homes, but there was no difference between the groups in Der p 1 levels, compared with baseline. CONCLUSIONS: The addition of MHRV to house dust mite eradication strategies did not achieve a reduction in mite allergen levels, but did improve evening PEF.

Effects of atorvastatin added to inhaled corticosteroids on lung function and sputum cell counts in atopic asthma.

BACKGROUND: Statins have anti-inflammatory properties that may be beneficial in the treatment of asthma. A study was undertaken to test the hypothesis that atorvastatin added to inhaled corticosteroids improves lung function and airway inflammation in atopic adults with asthma. METHODS: 54 adults with atopic asthma were recruited to a double-blind randomised controlled crossover trial comparing the effect of oral atorvastatin 40 mg daily with that of a matched placebo on asthma control and airway inflammation. Each treatment was administered for 8 weeks separated by a 6-week washout period. The primary outcome was morning peak expiratory flow (PEF). Secondary outcomes included forced expiratory volume in 1 s, asthma control questionnaire score, airway hyper-responsiveness to methacholine, induced sputum cytology and inflammatory biomarkers. RESULTS: At 8 weeks the change in mean morning PEF compared with baseline did not differ substantially between the atorvastatin and placebo treatment periods (mean difference -0.5 l/min, 95% CI -10.6 to 9.6, p = 0.921). Values for other clinical outcomes were similar between the atorvastatin and placebo treatment periods. The absolute sputum macrophage count was reduced after atorvastatin compared with placebo (mean difference -45.0 x 10(4) cells, 95% CI -80.1 to -9.7, p = 0.029), as was the sputum fluid leucotriene B4 (mean difference -88.1 pg/ml, 95% CI -156.4 to -19.9, p = 0.014). CONCLUSION: The addition of atorvastatin to inhaled corticosteroids results in no short-term improvement in asthma control but reduces sputum macrophage counts in mild to moderate atopic asthma. The change in sputum macrophage count suggests potential areas for investigation of statins in other chronic lung diseases.

Role of symptoms and lung function in determining asthma control in smokers with asthma.

BACKGROUND: Cigarette smoking in asthma increases the severity and accelerates the decline in lung function. The relative role of symptoms and lung function in determining asthma control in smokers with asthma is not known. AIM OF THE STUDY: The aim of this study was to compare asthma control in smokers vs never-smokers with asthma, using the validated Juniper asthma control questionnaire (ACQ), and assess if any difference was because of a particular symptom or the forced expiratory volume in one second (FEV(1)) value. METHODS: This was a cross-sectional study of 134 asthmatics (74 never-smokers and 60 smokers) with >or=15% reversibility in FEV(1) after salbutamol. All subjects completed the ACQ, recording FEV(1) and asthma symptoms (night awakening, morning symptoms, dyspnoea, wheeze, activity limitation and use of reliever inhaler). RESULTS: Compared with the never-smokers, smokers with asthma had significantly worse median (IQR) total asthma control score [1.6 (1.1-2.3) vs 2.8 (1.7-3.4); (P < 0.0001)] and in each of the six individual symptom question scores (P < 0.001), but no difference in FEV(1) levels (P = 0.908). CONCLUSION: Asthma control is significantly worse in asthmatics who smoke compared with never-smokers, with all symptoms related to asthma control uniformly worse in smokers, independent of FEV(1).

Smoking and airway inflammation in patients with mild asthma.

STUDY OBJECTIVES: Cigarette smoking is common in asthmatic patients, and we investigated the impact of cigarette smoking on airway inflammation in asthma. DESIGN: Single-center observational study of airway inflammation in asthmatic and healthy smokers and nonsmokers. SETTING: Asthma research unit in a university hospital. PATIENTS OR PARTICIPANTS: Sixty-seven asthmatic and 30 nonasthmatic subjects classified as smokers or nonsmokers. Asthmatics had chronic, stable asthma and were not receiving inhaled or oral steroids at the time of the study. INTERVENTIONS: We examined induced-sputum cell counts and levels of interleukin (IL)-8 and eosinophilic cationic protein (ECP). Bronchial hyperreactivity was assessed using methacholine challenge. MEASUREMENTS AND RESULTS: Asthmatic smokers had higher total sputum cell counts than nonsmoking asthmatics and both smoking and nonsmoking healthy subjects. Smoking was associated with sputum neutrophilia in both asthmatics and nonasthmatics (median, 47% and 41%, respectively) compared with nonsmokers (median, 23% and 22%, respectively), and sputum IL-8 was increased in smokers compared with nonsmokers, both in subjects with asthma (median, 945 pg/mL vs 660 pg/mL, respectively) and in healthy subjects (median, 1,310 pg/mL vs 561 pg/mL, respectively). Sputum eosinophils and ECP levels were higher in both nonsmoking and smoking asthmatics than in healthy nonsmokers. In smoking asthmatics, lung function (FEV(1) percent predicted) was negatively related to both sputum IL-8 (r = - 0.52) and sputum neutrophil proportion (r = - 0.38), and sputum IL-8 correlated positively with smoking pack-years (r = 0.57) and percent neutrophil count (r = 0.51). CONCLUSIONS: In addition to the eosinophilic airway inflammation observed in patients with asthma, smoking induces neutrophilic airway inflammation; a relationship is apparent between smoking history, airway inflammation, and lung function in smoking asthmatics.

Measurement of serum arabinitol by gas-liquid chromatography: limitations for detection of systemic candida infections.

The measurement of serum arabinitol in the diagnosis of systemic candidosis was evaluated using a gas-liquid chromatography technique in a cohort of at risk patients. The prevalence of seropositivity was low and did not correlate with evidence of infection. This technique is unlikely to achieve acceptance because it does not discriminate between patients with and without infection; it requires specialised equipment and it is expensive.

Fucose-specific adhesins on germ tubes of Candida albicans.

Lectin-like adhesins of hyphal-form Candida albicans were investigated by conventional fluorescence microscopy, fluorescence microscopy with image analysis, spectrofluorimetry and flow cytometry. Labelling was done with neoglycoprotein probes consisting of sugars (fucose, mannose, glucose, galactose, lactose) covalently linked to bovine serum albumin (BSA), which itself was labelled with fluorescein. The fucose probe bound to both the yeast and germ-tube portions of hyphal-form cells, not especially at the tip, but in the adjacent region of the germ-tube portion. Probes with the other sugars did not label the hyphal-form cells. Fucose-probe binding to the cells was optimal at pH 5.0 in citrate buffer, and was a time-dependent reaction requiring 30-60 min and reaching saturation concentration at 100 microg ml(-1). Each hyphal-form cell of C. albicans grown in 199 medium was calculated to have about 2 x 10(7) fucose probe-binding sites. There appeared to be no requirement for Ca2+ or Mg2+ in binding. Binding of the fucose probe to the hyphal-form cells was higher at 37 degrees C than at 22 degrees C or 4 degrees C. Fluorescence intensity of the fucose-labelled yeast forms was not increased over the hyphal-form cells. A germ-tube-deficient mutant when exposed to hyphal-form growth conditions for 2 h showed much less binding of the fucose probe than the wild-type which produced germ tubes. Confirmation of specificity and the need for a carrier molecule was obtained by showing that Fuc-BSA (without fluorescein) effectively inhibited the binding of the fucose probe, although L-fucose itself was inactive, as was Gal-BSA.

Pulmonary abnormalities in Crohn's disease.

Abnormalities of pulmonary function in Crohn's disease have been described, although the results are conflicting and anecdotal accounts of lung involvement are few. In this study we assessed the prevalence of lung function abnormalities in Crohn's disease, and the relative contributions of age, sex, smoking and past medical history, and Crohn's disease activity to the pulmonary abnormalities found. Twenty-nine patients with Crohn's disease and 29 age-, sex- and smoking-matched volunteer controls underwent detailed respiratory assessment. Airways obstruction due to chronic bronchitis and asthma was present in 13 patients with Crohn's disease, but was not more prevalent than in the control group. FEV1 was similar in both Crohn's disease and control subjects (84.2 +/- 21.2% predicted, mean +/- SD; 93.7 +/- 16.3%, respectively: n.s.). The vital capacity was significantly lower in the Crohn's disease patients than in controls (86.7 +/- 16.6%; 95.9 +/- 12.7%; P less than 0.01), but this may have been influenced by the higher prevalence of past or intercurrent medical illnesses affecting the chest in Crohn's disease patients. No patient had evidence of fibrosing alveolitis or bronchiectasis. The haemoglobin corrected transfer factor was significantly lower in the Crohn's disease patients than in controls (100.4 +/- 17.4%; 113.2 +/- 25.1: P less than 0.05) but the diffusing coefficient was not significantly different. There was a significant correlation (r = 0.44, P less than 0.05) between the residual volume and the Crohn's disease activity index but otherwise no close relationship was observed between Crohn's disease activity, extent or duration and the indices of lung function. These findings suggest that the lungs are relatively unaffected by Crohn's disease.

A comparison of the seroepidemiology of chlamydial infection in pigeon fanciers and farmers in the U.K.

A detailed comparative seroepidemiological study of antibody responses was performed in 271 pigeon fanciers and 100 farmers. Overall 73% of pigeon fanciers had IgG antibodies at a titre greater than or equal to 16 to Chlamydia pneumoniae, 39% to Chlamydia psittaci, and 6.6% to Chlamydia trachomatis. The prevalence of chlamydial antibodies was significantly lower in the farmers at 47% for C. pneumoniae, 6% for C. psittaci, and 2% for C. trachomatis. Both populations were exposed to complex microbiological and antigenic environments: 50.5% of the pigeon fanciers had antibodies to pigeon antigens, 34% to egg membrane, and 0.73% to yolk sac antigen, and 59% of the farmers had antibodies to Micropolyspora faeni, but the high prevalence of chlamydial antibodies could not be attributed to interaction with these antigens. There was considerable overlap of chlamydial antibody responses in the pigeon fanciers but not in the farmers: 36% of the pigeon fanciers had antibodies to C. pneumoniae alone, 5% to C. psittaci alone, and 31% to both agents, whereas only 3% of farmers had antibodies to both C. pneumoniae and C. psittaci. The high prevalence of antibodies to C. psittaci in the pigeon fanciers is compatible with the known avian reservoir for this infection. The particularly high prevalence of antibodies to C. pneumoniae suggests that complex interactions may be occurring in a population exposed to two chlamydial organisms, whereby infection with one species may provoke an anamnestic response against other chlamydial organisms with which the subject has previously been infected.

The recent impact of antiretroviral combination therapy on CD4 counts, AIDS and death in HIV-infected persons: routine HIV surveillance in Scotland.

Our aim was to investigate if the clinical benefits of combination antiretroviral therapy recently reported from clinical trials are reproduced in a population-based HIV surveillance scheme. This surveillance scheme is estimated to cover 90% of the HIV-positive population currently under immunological monitoring in Scotland. Our results showed a considerable reduction in new AIDS cases among this group from 107 in 1995 to 59 in 1996 and an estimated 58 in 1997 (allowing for reporting delay). There was a similar fall in deaths from 75 in 1995 to 59 in 1996 and an estimated 24 in 1997. These observations are temporally associated with increasing prescription of antiretroviral therapy in Scotland throughout 1996 and 1997. Examination of those individuals monitored in both 1996 and 1997 showed that from their first CD4 count in 1996 to their first count in 1997 there has been a median gain of 6 CD4 cells/mm3 (95%CI 0-12) compared with a median fall of 27 CD4 cells/mm3 (95%CI -35, -17) for those monitored in both 1995 and 1996. Highest median gains in CD4 cell counts from 1996 to 1997 were seen in those receiving triple or quadruple therapy (median gain 32CD4 cells/mm3). These results are further strengthened by the results of a separate longitudinal analysis showing a highly significant (P < 0.001) effect of treatment on CD4 cell loss with the highest mean CD4 gains being seen in those in triple or quadruple therapy. Our results indicate that the benefits of combination antiretroviral therapy previously seen in clinical trials are being reproduced at a population level. It remains to be seen if these benefits can be sustained in the long term.

Serum IgG and IgE antibody against aerosolised antigens from Nephrops norvegicus among seafood process workers.

Employees in a seafood factory developed high titers of serum IgE and IgG antibody to antigens from prawn (N. norvegicus) which were aerosolized during processing. Significant serum IgE antibody titers occurred only among those subjects with occupation-related respiratory symptoms, and this serological parameter may be a useful clinical adjunct in the investigation of this disease. Serum IgG antibody was detected with equal frequency and titer in symptomatic and asymptomatic workers. There was no significant correlation between either antibody class response and the individual's age or years of work exposure. Cigarette smoking, however, was positively associated with the IgE antibody response, and negatively associated with the IgG antibody response to the same inhaled antigen. Investigating the effects of smoking at the mucosal level in the lung may provide insight into how the lung processes and responds to inhaled antigens.

Randomised controlled trial of homoeopathy versus placebo in perennial allergic rhinitis with overview of four trial series.

OBJECTIVE: To test the hypothesis that homoeopathy is a placebo by examining its effect in patients with allergic rhinitis and so contest the evidence from three previous trials in this series. DESIGN: Randomised, double blind, placebo controlled, parallel group, multicentre study. SETTING: Four general practices and a hospital ear, nose, and throat outpatient department. PARTICIPANTS: 51 patients with perennial allergic rhinitis. INTERVENTION: Random assignment to an oral 30c homoeopathic preparation of principal inhalant allergen or to placebo. MAIN OUTCOME MEASURES: Changes from baseline in nasal inspiratory peak flow and symptom visual analogue scale score over third and fourth weeks after randomisation. RESULTS: Fifty patients completed the study. The homoeopathy group had a significant objective improvement in nasal airflow compared with the placebo group (mean difference 19.8 l/min, 95% confidence interval 10.4 to 29.1, P=0.0001). Both groups reported improvement in symptoms, with patients taking homoeopathy reporting more improvement in all but one of the centres, which had more patients with aggravations. On average no significant difference between the groups was seen on visual analogue scale scores. Initial aggravations of rhinitis symptoms were more common with homoeopathy than placebo (7 (30%) v 2 (7%), P=0.04). Addition of these results to those of three previous trials (n=253) showed a mean symptom reduction on visual analogue scores of 28% (10.9 mm) for homoeopathy compared with 3% (1.1 mm) for placebo (95% confidence interval 4.2 to 15.4, P=0.0007). CONCLUSION: The objective results reinforce earlier evidence that homoeopathic dilutions differ from placebo.

Intergenerational 20 year trends in the prevalence of asthma and hay fever in adults: the Midspan family study surveys of parents and offspring.

OBJECTIVE: To estimate trends between 1972-6 and 1996 in the prevalences of asthma and hay fever in adults. DESIGN: Two epidemiological surveys 20 years apart. Identical questions were asked about asthma, hay fever, and respiratory symptoms at each survey. SETTING: Renfrew and Paisley, two towns in the west of Scotland. SUBJECTS: 1,477 married couples aged 45-64 participated in a general population survey in 1972-6; and 2,338 offspring aged 30-59 participated in a 1996 survey. Prevalences were compared in 1,708 parents and 1,124 offspring aged 45-54. MAIN OUTCOME MEASURES: Prevalences of asthma, hay fever, and respiratory symptoms. RESULTS: In never smokers, age and sex standardised prevalences of asthma and hay fever were 3.0% and 5.8% respectively in 1972-6, and 8.2% and 19. 9% in 1996. In ever smokers, the corresponding values were 1.6% and 5.4% in 1972-6 and 5.3% and 15.5% in 1996. In both generations, the prevalence of asthma was higher in those who reported hay fever (atopic asthma). In never smokers, reports of wheeze not labelled as asthma were about 10 times more common in 1972-6 than in 1996. With a broader definition of asthma (asthma and/or wheeze), to minimise diagnostic bias, the overall prevalence of asthma changed little. However, diagnostic bias mainly affected non-atopic asthma. Atopic asthma increased more than twofold (prevalence ratio 2.52 (95% confidence interval 1.01 to 6.28)) whereas the prevalence of non-atopic asthma did not change (1.00 (0.53 to 1.90)). CONCLUSION: The prevalence of asthma in adults has increased more than twofold in 20 years, largely in association with trends in atopy, as measured indirectly by the prevalence of hay fever. No evidence was found for an increase in diagnostic awareness being responsible for the trend in atopic asthma, but increased awareness may account for trends in non-atopic asthma.

Pulmonary hypersensitivity in the alginate industry.

Salts of alginic acid are complex polymerised polysaccharides which are chemically extracted from seaweed. Workers in the alginate industry are exposed to dust from dried milled seaweed and pure alginate compounds. In this survey of one of the two factories in Britain producing alginates, we found evidence of pulmonary hypersensitivity to seaweed dust in seven per cent of the total work force, and evidence of precipitating antibody to sodium alginate and seaweed extracts in the serum of 4.5 per cent of the work force. Challenge testing of a number of employees with symptoms showed a dual response with immediate airways obstruction, and a later loss of lung volume, with associated impairment of transfer factor.