职业性哮喘患者肺功能变化的临床观察

目的了解职业性哮喘患者的肺功能变化特点。方法对15例职业性哮喘患者行支气管现场激发试验时的肺功能参数进行分析,并同时记录发生时间及患者症状、体征。结果①发作期和激发前肺功能值比较,大部分肺功能参数差异有统计学意义(P0.05)。发作期用力肺活量(FVC)、第1秒用力呼气容量(FEV1)、最大用力呼气流速(PEF)、最大呼气中段流速(MMEF)、25%和50%肺活量时的最大呼气流速(FEF25、FEF50)显著低于激发前;②经直线相关分析,FEV1与FVC下降率之间,FEF50与MMEF下降率之间以及FEV1与MMEF下降率之间均呈直线相关(rs=0.825,P=0.006;rs=0.992,P=0.000;rs=0.881,P=0.004)。③激发后60 min内现场支气管激发试验阳性10例,且全部出现全身发汗、颜面发绀及肺部哮鸣音等严重临床表现,占67%;激发2 h后的现场支气管激发试验阳性5例,占33%。结论职业性变应原致使患者的大小气道功能受限,职业性哮喘可呈速发相反应或迟发相反应。呈速发相反应患者的临床表现明显。     

Specific inhalation challenge with wheat flour in workers with suspected baker's asthma

Objective: The aim of this study was to evaluate the outcome of the specific inhalation challenge test (SIC) in 160 subjects with suspected baker's asthma and to assess its relation to total flour dust levels and to personal characteristics such as specific skin sensitisation, non-specific bronchial hyper-responsiveness (NSBH) and atopy. Methods: We investigated the outcome of SIC tests performed with wheat flour in six Italian laboratories. For each subject, data was available regarding skin sensitisation to wheat flour, NSBH, atopy, forced expiratory volume at 1 s (FEV1) monitoring and airborne flour dust in the challenge chamber measured by the gravimetric method (total dust in mg/m³). Results: The SIC test was positive for early asthma in 42 subjects (26%) and for late/dual asthma in 18 (11%). Positive outcome to SIC was significantly associated with NBSH (odds ratio, OR: 3.5, 95% CI: 1.6–7.7) and skin sensitisation to wheat flour (OR: 3.1, 95% CI: 1.3–7.0). Exposure level to wheat flour was less than or equal to 10 mg/m³ in 12% of individuals, ranged between 11 and 30 mg/m³ in 43% and exceeded 30 mg/m³ in 45%. The outcome of SIC was always negative among workers not skin sensitised to wheat flour and without NSBH and atopy. An increasing prevalence of positive SIC was observed among workers with one or more of the above-mentioned personal characteristics whose challenge exposure was greater than 10 mg/m³ (P < 0.001). Conclusion: Procedures currently adopted for wheat flour dust exposure during SIC need to be better standardised in order to avoid excessive airborne dust exposure. Over-exposure seems to be of no use for the diagnosis and risks making the asthmatic reaction worse, particularly in patients who are both sensitised to wheat allergens and have NSBH and/or atopy. Received: 12 August 1998 / Accepted: 19 March 1999     

Occupational asthma related to low levels of airborne methylene diphenyl diisocyanate (MDI) in orthopedic casting work

Orthopedic plaster casts contain methylene diphenyl diisocyanate (MDI). A few case reports have suggested occupational asthma to MDI in casting work. However, the knowledge of the exposure levels related to the occupational asthma cases is lacking. We report on two occupational asthma cases due to MDI in nurses irregularly applying orthopedic plaster casts, verified with placebo controlled specific inhalation challenge. The levels of MDI in the air were measured in the exposure chamber during the specific inhalation challenges with a quantitative method including filter collection and subsequent liquid chromatography-mass spectrometry (LC-MS) analysis of the isocyanate groups. In order to estimate the level of airborne MDI in casting work, measurements were conducted also in two hospitals during the application and removal of synthetic plaster casts using the same method. The concentrations were well below the occupational exposure limit in both specific inhalation challenge and hospital measurements. Based on our findings, even minor exposure to airborne MDI in casting work can cause an asthmatic reaction in some patients.     

Case report of occupational asthma due to palisander wood dust and bronchoprovocation challenge by inhalation of pure wood dust from a capsule

Occupational asthma due to exposure to exotic wood dust and to rosewood (Dalbergia family) has been reported earlier. This paper deals with a case of occupational asthma due to palisander wood dust (Dalbergia nigra) in a joiner who sanded and polished parts of musical instruments. The causal relationship was confirmed by a positive skin reaction to an allergenic preparation and a positive nonimmediate, late asthmatic reaction after inhalation challenge testing with pure palisander wood dust. A method of bronchoprovocation testing with an occupational allergen is presented. It proved to be a practical and advantageous method in its simplicity and single-blind application of placebo. It should, however, be used with great caution, in well-chosen cases in whom nonspecific bronchial reactivity is proved or recorded to be in normal ranges.     

Baker's asthma with a predominant clinical response to rye flour

BACKGROUND: Relatively little attention has been paid to rye flour as opposed to wheat flour in clinical and epidemiological research into Baker's asthma. METHODS: This report describes the investigation of a baker with asthma who reported a workplace response to rye flour and none to wheat flour, despite co-reactivity to both wheat and rye antigen. RESULTS: Skin prick tests, RASTs and basophil stimulation tests were positive for both wheat and rye antigen, but quantitatively greater for rye than wheat. Bronchial challenge elicited a much greater response to the rye-wheat flour mix used in the bakery than to 100% wheat flour. CONCLUSIONS: The greater clinical response to rye than to wheat may be immunologically mediated, but could also be due to physical characteristics of rye flour such as greater dose of inhaled airborne particles or an irritative effect. This information may be useful for medical management and occupational hygiene control, and should stimulate further research into rye flour in Baker's asthma.     

Relation between occupational asthma case history,bronchial methacholine challenge,and specific challenge test in patients with suspected occupational asthma

Inhalative methacholine challenge (MC) was performed in 229 subjects presumed to suffer from occupational asthma due to exposure to airborne latex allergens (n = 62), flour (n = 28), isocyanates (n = 114), or irritants in hairdressers' salons (n = 25). They were also subjected to specific challenges with the occupational agents they were exposed to, completed a questionnaire using an abbreviated version of the ATS-DLD, and were interviewed by an experienced physician. Bronchial hyperresponsiveness in MC was defined by the results obtained in a previous study with 81 healthy volunteers. The threshold in these controls was set at a cumulative MC dose of 0.3 mg, corresponding to a sensitivity of 95%. The main purpose of the study was to investigate whether the MC and/or the occupational asthma case history are reliable predictors of the specific challenge test outcomes. In 40–72% of examined subjects, workplace-related asthma complaints occurred, with bronchial hyperreactivity in the MC ranging from 48% to 61%. However, only 12–25% demonstrated a significant bronchoconstructive reaction in the specific challenge test. MC results are only moderately associated with workplace-related asthma case histories. Positive outcomes of challenges with occupational agents are well correlated with positive MC results plus occupational asthma case histories. The combination of MC and occupational asthma case history shows a relatively high specifity (62%, 86%, 80%), but the sensitivity was moderately low (83%, 71%, 52%). MC sensitivities were 92%, 71%, and 62% (case histories of hairdressers were not available). We conclude that in most cases, occupational asthma (as defined by a specific challenge test response) is combined with bronchial hyperresponsiveness and workplace-related asthmatic symptoms. However, subjects of each exposure group demonstrated bronchial hyperresponsiveness and complained of workplace-related asthmatic symptoms, but occupational asthma could not be proved in the specific challenge test. In subjects with a positive occupational asthma case history, a negative MC test result can almost rule out a positive specific challenge test result. Hence, the MC test can reduce performance of the laborious specific challenge test. Am. J. Ind. Med. 33:114–122, 1998. © 1998 Wiley-Liss, Inc.     

Association of pediatric asthma severity with exposure to common household dust allergens

Background

Reducing exposure to household dust inhalant allergens has been proposed as one strategy to reduce asthma.

Objective

To examine the dose-response relationships and health impact of five common household dust allergens on disease severity, quantified using both symptom frequency and medication use, in atopic and non-atopic asthmatic children.

Methods

Asthmatic children (N=300) aged 4-12 years were followed for 1 year. Household dust samples from two indoor locations were analyzed for allergens including dust mite (Der p 1, Der f 1), cat (Fel d 1), dog (Can f 1), cockroach (Bla g 1). Daily symptoms and medication use were collected in monthly telephone interviews. Annual disease severity was examined in models including allergens, specific IgE sensitivity and adjusted for age, gender, atopy, ethnicity, and mother's education.

Results

Der p 1 house dust mite allergen concentration of 2.0 μg/g or more from the main room and the child's bed was related to increased asthma severity independent of allergic status (respectively, OR 2.93, 95% CI 1.37, 6.30 for 2.0-10.0 μg/g and OR 2.55 95% CI 1.13, 5.73 for ?10.0 μg/g). Higher pet allergen levels were associated with greater asthma severity, but only for those sensitized (cat OR 2.41 95% CI 1.19, 4.89; dog OR 2.06 95% CI 1.01, 4.22).

Conclusion

Higher levels of Der p 1 and pet allergens were associated with asthma severity, but Der p 1 remained an independent risk factor after accounting for pet allergens and regardless of Der p 1 specific IgE status.     

Role of skin prick test and serological measurement of specific IgE in the diagnosis of occupational asthma resulting from exposure to vinyl sulphone reactive dyes

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<0.05). In four patients with occupational asthma from reactive dyes and eight control subjects exposed to reactive dye, IgE specific to reactive dye conjugated to HSA was detected with ELISA even though they showed negative skin reactivity. Six patients completely avoided the reactive dye for a mean (SD) 27.8 (10.3) months, IgE specific to reactive dyes decreased in all six patients (p<0.05) during this time.
CONCLUSIONS—Both SPTs and detection of IgE specific to reactive dye in serum samples could be valuable for screening, diagnosis, and monitoring occupational asthma resulting from exposure to reactive dyes. These two tests would complement each other.


Keywords: reactive dye; occupational asthma; skin prick test     

46例儿童咳嗽变异性哮喘的呼吸阻抗肺功能测定及过敏原检测分析

目的:探讨儿童咳嗽变异性哮喘(CVA)的肺功能特征及过敏原检测结果的特征。方法:选择46例儿童CVA患者作为研究组,同时选取同期就诊的急性支气管炎患儿25例作为对照组,两组患儿同时进行了呼吸阻抗肺功能检测及过敏原皮肤点刺检测,另外对于气道阻力增高者加做支气管舒张试验。结果:CVA患儿均存在气道阻力不同程度的增高,其阻力增高程度与对照组相比有显著差异,气道阻力增高者舒张试验阳性率为75%,CVA组过敏原检测的阳性率与急性支气管炎组相比较有显著差异。结论:CVA患儿大部分有可逆性气道阻塞,并且其发病与过敏因素关系密切,因此对长期慢性咳嗽患儿进行肺功能检测及过敏原检测有助于明确病因诊断。     

A new case of occupational asthma from reactive dyes with severe anaphylactic response to the specific challenge.

A case of occupational asthma in a wool and cotton dyer handling reactive dyes is described. The patient was skin positive, but asymptomatic to house dust mites. A bromoacrilamidic dye (Lanasol Yellow 4G) has been identified through chamber inhalation challenge as being responsible for the sensitization. A very short (4-minute) exposure produced a severe immediate obstructive ventilatory defect followed by arterial hypotension and urticaria. Bronchial hyperresponsiveness as tested through metacholine challenge was absent both in basal conditions and after the dye challenge. Both prick and patch test for the dye were positive in the absence of any sign of contact dermatitis.     

糖皮质激素对COPD与支气管哮喘患者气道炎症影响的探讨

目的探讨慢性阻塞性肺疾病(COPD)和支气管哮喘患者外周血白细胞介素4(IL-4)、白细胞介素8(IL-8)、白细胞介素10(IL-10)水平及其受糖皮质激素的影响。方法采用双抗体夹心酶联免疫吸附法(ELISA)分别检测了急性发作期COPD患者50例(COPD组)、急性发作期哮喘患者50例(哮喘组)给予糖皮质激素治疗前后和健康志愿者(正常对照组)血清中IL-4、IL-8、IL-10的水平,对结果进行统计学分析。结果 (1)COPD组和哮喘组急性发作期IL-4、IL-8水平明显高于缓解期和正常对照组(p<0.01),给予糖皮质激素治疗以后,IL-4、IL-8水平明显降低,但仍高于正常对照组(p<0.01);急性发作期COPD组IL-4明显低于哮喘组IL-4水平(p<0.01),IL-8明显高于哮喘组IL-8水平(p<0.01)。(2)COPD组和哮喘组急性发作期IL-10水平明显低于缓解期和正常对照组(p<0.01),给予糖皮质激素治疗以后,IL-10水平明显升高,但仍低于正常对照组(p<0.01);急性发作期COPD组IL-10明显高于哮喘组IL-10水平(p<0.01)。结论 (1)IL-4、IL-8、IL-10是参与COPD和哮喘气道炎症反应的重要细胞因子。(2)IL-4、IL-8是促炎因子,而IL-10是抑炎因子。(3)糖皮质激素可以下调COPD和哮喘急性发作期患者血清IL-4、IL-8水平,而促进IL-10水平的升高,进而减轻气道炎症反应,更快地改善临床症状。     

Analysis of the clinical state of patients with occupational asthma following cessation of exposure to allergens

The purpose of this study was to evaluate the health state of patients with occupational asthma after cessation of occupational exposure to bakery allergens. A follow-up study of 56 subjects with occupational asthma was carried out. Subjects were examined twice: 1-6 months after removal from occupational exposure and 36 or 48 months later. Clinical state analysis both at diagnosis and re-examination was performed with the use of a questionnaire. Functional spirometric tests and skin prick tests and/or specific serum IgE were carried out during both examinations at points of time at which the subjects regarded their asthma symptoms as least severe. According to the subjective evaluation of the patients' clinical state, some improvement could be noticed 36 or 48 months after removal from work. Forced expiratory volume in one second (FEV1) and peak respiratory flow (PEF) did not change significantly. Total serum IgE concentration decreased in only two subjects, but the mean value of total IgE level did not significantly differ at the first and second examination after the cessation of occupational exposure. There was no significant difference in the number of positive skin prick tests to common and occupational allergens between the first and second examination. The majority of patients with occupational asthma reporting subjectively on their symptoms indicated an improvement in their clinical state 2-3 years after removal from occupational exposure. The intensity of skin prick tests was not reduced in the studied group. Non-specific bronchial hyper-responsiveness was not reduced in the majority of subjects with occupational asthma at least 2 years after cessation of occupational exposure.     

Expectations of patients and parents of children with asthma regarding access to complementary therapy information and services via the NHS: a qualitative study

OBJECTIVE: To explore the expectations of patients and parents of children with asthma regarding access to complementary therapies via the NHS. METHODS: Fifty semi-structured interviews with adults and parents of children with asthma, from a range of health-care settings, including users and non-users of complementary therapies. Interviews were recorded, transcribed verbatim and the data were analysed thematically. RESULTS: Thirty-one patients were using complementary therapies for asthma, six were using complementary therapies for other health problems and 13 were non-users. Various therapies were used for asthma, most commonly homeopathy and breathing techniques, predominantly outside the NHS. Two broad themes emerging from the data were expectations about access to information and knowledge about complementary therapies via NHS health professionals, and expectations regarding access to complementary therapy services via the NHS. As a minimum, the majority of participants wanted NHS health professionals to be more 'open' towards and know more about complementary therapies than their patients - perceived as not currently usual. Most were positive about greater NHS access to complementary therapy services, for enhancing patient choice, improving equality in access for less affluent patients and facilitating patients' self-help. Participants who were highly sceptical about complementary therapies argued that lack of scientific evidence of effectiveness prohibited the need for greater complementary therapy knowledge or service provision within the NHS. Alongside their expectations, patients and parents expressed realistic views about facilitators and barriers to greater access. CONCLUSIONS: While health service planners and providers often express reservations about the value of complementary therapies, it is important to take patients' preferences into account if policy discourses regarding patient-centred care and choice are to be realized in practice.     

Allergic patients with and without allergen-specific immunotherapy mount protective immune responses to tick-borne encephalitis vaccination in absence of enhanced side effects or propagation of their Th2 bias

BackgroundAllergic diseases are caused by Th2-driven immune responses and their treatment with specific immunotherapy (SIT) leads to immunomodulation via IL10, TGF-ß and Th1/Tr1 shift. This phase IV, open-label clinical trial investigated whether allergies and SIT treatment influenced immune responses to routine vaccination.MethodsWe studied three groups: 49 allergic patients (allergic group), 21 allergic patients receiving maintenance doses of SIT (SIT group), and 49 non-allergic controls. All subjects received tick-borne encephalitis (TBE) booster vaccines and humoral and cellular immune responses were evaluated after one week, four weeks and six months.ResultsThe levels and kinetics of neutralizing TBE-specific antibodies, reflecting protection against TBE, were not significantly different in the three groups. The allergic group showed Th2 polarization pre-booster as indicated by increased TBE-specific IgG1 and elevated mitogen-induced IL5 production. Alum-adjuvanted TBE vaccine led to Th2 biased immune responses in the controls, but to no further enhancement of Th2 polarization in the allergic and SIT group. Furthermore, in the SIT group cellular parameters reflected the induction of immunomodulation due to increased Tregs, elevated baseline IL10 and lack of TBE-specific IL5. Importantly, these cellular regulatory responses did not limit the ability to mount sufficient TBE-specific antibodies after the booster. All groups tolerated the vaccine well with no exacerbation of allergic symptoms.ConclusionTBE booster vaccinations were immunogenic and safe in both the allergic and SIT group and contributed to balanced immune responses. Our data indicate that all allergic patients, even when undergoing SIT, should be vaccinated without hesitation and at regular intervals according to standard recommendations.ClinicalTrials.gov (NCT02511535).     

Serologic response to meningococcal vaccination in patients with cold agglutinin disease (CAD) in the novel era of complement inhibition

Cold agglutinin disease (CAD) is a rare, potentially life-threatening acquired autoimmune hemolytic anemia characterized by hemagglutination and hemolysis due to immunoglobulin-mediated (usually IgMκ) classic complement pathway activation. Complement inhibition (CI) represents a novel treatment option to control hemolysis. Due to CI patients (pts) are susceptible to encapsulated bacteria e.g. N. meningitidis. Therefore, meningococcal vaccination on CI is mandatory. In this study serologic response to the tetravalent conjugate vaccine Menveo® was analyzed in CAD pts on eculizumab treatment (DECADE trial) using rabbit serum as complement source (rSBA). Protective rSBA titers varied for meningococcal serogroups and over time reflecting an early decline to even non-protective rSBA titers. These data highlight the importance of serologic analyses under chronic CI. Currently, re-vaccination with a tetravalent meningococcal conjugate vaccine every 3 years is recommended on chronic CI. However, re-vaccination on CI might further rely on serologic analyses, implying even early booster vaccinations similar to adults with (functional) asplenia.