Extrinsic allergic alveolitis caused by misting fountains

Recently, an increasing number of patients were presented to our clinics with febrile and respiratory symptoms associated with exposure to a new type of domestic ultrasonic humidifier. We report on 11 patients who developed recurrent episodes of fever, cough and dyspnea after repeated exposure to ultrasonic misting fountains at home. A diagnosis of extrinsic allergic alveolitis (EAA) or toxic alveolitis was made on the basis of the history and the clinical, radiological, laboratory and immunological findings. Eight patients were subjected to inhalative challenge tests with their own ultrasonic misting fountains, and all of them exhibited positive reactions. Nine patients were diagnosed with an EAA (humidifier lung) and two patients with a toxic alveolitis (humidifier fever). This study demonstrates the potential for ultrasonic misting fountains to cause illness in the home. In view of the increasing popularity of these devices, humidifier lung and humidifier fever should be considered in the differential diagnosis of patients with unexplained pulmonary or flu-like illnesses with fever.     

Extrinsic allergic alveolitis induced by the yeast Debaryomyces hansenii.

A 65-yr-old female developed cough, fever and dyspnoea following repeated exposure to a home ultrasonic humidifier. High-resolution computed tomography showed ground-glass opacity in both lung fields. Arterial blood gas analysis gave an oxygen tension of 8.38 kPa (63 Torr). Pulmonary function testing revealed restrictive ventilatory impairment with a reduction in the diffusing capacity. The diagnosis of extrinsic allergic alveolitis (EAA) was confirmed by radiographic findings, pathological evidence of alveolitis and reproductive development by a provocation test to the humidifier water. The yeast Debaryomyces Hansenii was the only microorganism cultured from the water of the humidifier. The double diffusion precipitating test and lymphocyte proliferative response was positive for an extract of D. Hansenii, providing evidence to incriminate this fungus. This is the first described case of EAA caused by D. Hansenii.     

Proteolytic activities in bronchoalveolar lavage fluid of interstitial lung diseases: correlation to stage and prognosis

In 18 patients with sarcoidosis, 10 patients with idiopathic pulmonary fibrosis (IPF), 6 patients with exogen allergic alveolitis (EAA), and 9 control persons we investigated proteolytic activities in bronchoalveolar lavage fluid (BALF). In lymphocyte-macrophage alveolitis (i.e. sarcoidosis and EAA) proteolytic activities in BALF were low, but the activities correlated with lung function deterioration within 1 year. In IPF (i.e. in neutrophil alveolitis) we found a striking correlation between proteolytic activities and stage of disease: high activities correlated with early stages, lower values with late stages of IPF. Measurement of proteolytic activity in BALF seems to be of interest to differential diagnosis and to prognosis of interstitial lung disease.     

Allergic alveolitis in a 12-year-old boy: treatment with budesonide nebulizing solution.

Allergic alveolitis due to bird antigens was diagnosed in a 12-year-old boy. He suffered from cough, dyspnea, easy fatigue, anorexia, and severe weight loss. The diagnosis was verified by a gradual improvement when he was removed from the birds, exacerbation upon re-exposure, and the demonstration of serum precipitating antibodies against bird antigens. The patient recovered completely after a short course of oral prednisolone, treatment with inhaled nebulized budesonide for 3 months, and removal of the birds from his home.     

外源性变应性肺泡炎的临床病理特征和影像学表现

目的探讨外源性变应性肺泡炎(EAA)的临床病理特征和影像学表现。方法分析5例外源性变应性肺泡炎病例的临床特点、影像学表现、肺活检的病理特征。结果 EAA常见的临床表现为咳嗽、呼吸困难、咳痰、发热;主要阳性体征为轻度紫绀、肺部听诊湿啰音或Velcro啰音;肺功能检查显示限制性通气功能障碍和弥散功能障碍。HRCT表现为磨玻璃影、小叶间隔增厚、小叶中心性结节、网格影和蜂窝肺等。支气管肺泡灌洗液显示淋巴细胞增多。肺活检组织病理学示淋巴细胞性间质性肺炎,细支气管周围可见小的不典型肉芽肿和多核巨细胞。患者对糖皮质激素治疗有效。结论临床表现结合影像学特点可提示EAA临床诊断,肺活检是诊断EAA有效的检查方法。     

Significance and role of radiation studies in complex diagnosis of exogenous allergic alveolitis

The authors highlight X-ray symptom complexes (XRSC) (emphysematointerstitial, parenchymatointerstitial, and pneumonic) which are characteristic of exogenous allergic alveolitis (EAA). The above XRSC are comparable with the clinical types of EAA. The semeiotics typical of each XRSC and the value of radiation diagnostic methods in specifying changes in lung tissue and intrathoracic lymph nodes, the activity of the process are presented. Each study (classical X-ray, CT, radionuclide scintigraphy) has its own advantages and resolution limits. Radiation studies in the diagnosis of EAA should be used purposefully in combination with other studies (immunology, external respiratory function test, bacterial cytology, morphology) by taking into account the clinical manifestations of the disease.     

Cytomorphologic changes detected in bronchial biopsy specimens in patients with alveolitis

Eighty-nine patients with alveolitis were followed up. Of them, 60 patients had exogenous allergic alveolitis (EAA) and 29 had idiopathic fibrosing alveolitis (IFA). Transbronchial lung biopsy (TLB) proved to be the most informative method for alveolitis. At the same time a cytomorphologic study of TLB specimens revealed exogenous allergic alveolitis in all phases of the disease in 91.2% of the cases. In idiopathic fibrosing alveolitis, the informative value of TLB was 59.7%.     

Some parameters of bronchoalveolar lavages in alveolitis

Eighty nine patients with alveolitis [60 with extrinsic allergic alveolitis (EAA) and 29 with idiopathic fibrosing alveolitis (IFA)] were followed up. Cytological and immunological studies of bronchoalveolar lavage revealed that the patients with EAA had elevated counts of lymphocytes, moderately increased neutrophils and eosinophils, decreased alveolar macrophages, elevated SIgA and T lymphocytes. In the patients with IFA, only higher counts of neutrophils were significant.     

Diagnostic aspects of allergic alveolitis

The clinical picture of extrinsic allergic alveolitis (EAA) or hypersensitivity pneumonitis is etiologically extremely multivarious and in disposed persons it can be caused by inhalation of proteins of various species of animals (in particular by avian proteins), mushrooms, bacteria, insects, thermoactinomycetes, vegetable antigens, possibly also haptens after fixation with protein produced inside the body. The inhaled dusts with a size particles of 4 to 5 micrometers which contain the disease-evoking antigens often have an activity-specific character which is expressed in the traditional names of individual forms of alveolitis (e.g. farmer's lung, mushroom-worker's lung, cheese-washer's lung, malt-worker's lung, bagassosis). However, according to our inquiries in the GDR as well as in other parts of Central and East Europe these diseases are relatively rare. In the GDR the so-called bird-fanciers' or bird-keepers' lung with a frequency of 83.4% has a supreme significance within all forms of alveolitis, followed by the farmer's lung (8.9%) and forms of alveolitis by mushrooms (7.7%). In a period of 10 years altogether 7,669 sera of patients with suspicion of alveolitis were investigated at our institute. According to the results of the immunological as well as of further paraclinical and clinical examinations in 550 cases the diagnosis of allergic alveolitis was made (459 bird-fancier's lungs, 49 farmer's lungs and 42 cases of allergic alveolitis by moulds). In 88.5% of the patients who fell ill with extrinsic allergic alveolitis the disease is accompanied by a positive or very positive antigen-specific antibody formation in the blood.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cockade-like structures in alveolar macrophages in extrinsic allergic alveolitis

BACKGROUND AND OBJECTIVES: In immunocytochemical preparations of bronchoalveolar lavage (BAL) cells from patients with extrinsic allergic alveolitis (EAA), we observed the presence of alveolar macrophages with cockade-like structures in their cytoplasm (cockade+ alveolar macrophages). These cockade+ alveolar macrophages may reflect a subpopulation of alveolar macrophages which may show a different predominance in various interstitial lung diseases. In this study we aimed to compare the frequency of cockade+ alveolar macrophages in patients with EAA (n = 14) with the results obtained in patients with sarcoidosis (n = 11), idiopathic interstitial pneumonia (IIP; n = 10) and control subjects (n = 8). We also investigated the expression of the transferrin receptor CD71 on cockade+ alveolar macrophages. METHODS: In BAL fluid, the total number of cells and differential counts were determined, and immunocytologic examinations of macrophages and lymphocytes were done using monoclonal antibodies. The percentage of cockade+ alveolar macrophages was determined by counting 300 macrophages in the CD20 field of an immunocytochemical slide. RESULTS: The percentage of cockade+ alveolar macrophages was significantly higher in the EAA group (36 +/- 9%) compared to patients with sarcoidosis (12 +/- 5%) or IIP (11 +/- 10%) and control subjects (3 +/- 1%; p < 0.001). The proportion of CD71+ alveolar macrophages was significantly lower in EAA than in the other groups (p < 0.01), and the CD71 antigen was expressed on a significantly lower proportion of cockade+ alveolar macrophages compared to cockade- alveolar macrophages in EAA (p < 0.001). CONCLUSION: We conclude that cockade+ alveolar macrophages could play a role in the pathogenesis and differential diagnosis EAA.     

The HRCT features of extrinsic allergic alveolitis

Exposure to organic dusts can produce an immune-mediated inflammatory response in sensitized individuals. The pulmonary disease caused by this response has been called extrinsic allergic alveolitis (EAA) or hypersensitivity pneumonitis. The clinical phases associated with this process have been termed acute, subacute, and chronic. There are corresponding imaging findings that are characteristic of each of these phases, although there is some overlap between the phases. The acute phase is characterized by confluent opacities that may mimic infection or edema. The subacute phase is characterized by centrilobular nodules, areas of ground-glass attenuation, a mosaic perfusion pattern, and air trapping on expiratory imaging. The chronic phase is characterized by subpleural irregular linear opacities with associated architectural distortion. Honeycombing may sometimes also be present. In the acute and subacute phases, the disease is predominantly in the lower lungs, whereas in chronic EAA the findings are predominant in the mid to upper lungs. Although the high-resolution computed tomography findings individually are nonspecific, the combination of the findings coupled with the distribution of the findings can often narrow the differential or allow a presumptive diagnosis of EAA to be made.     

Sequential bronchoalveolar lavage in experimental extrinsic allergic alveolitis. The influence of cigarette smoking

We studied the alterations induced by acute experimental extrinsic allergic alveolitis (EAA) on bronchoalveolar cell population in smoking and nonsmoking guinea pigs. Sixty-two animals divided into 3 groups were studied: Group 1 (17 animals), controls; Group 2 (21 animals), extrinsic alveolitis; Group 3 (24 animals), cigarette smoking and alveolitis. Bronchoalveolar lavages (BAL) were performed on Days 1, 19, and 44 for all animals. Group 3 animals had a fourth lavage before starting cigarette smoking, that is, 28 days before the beginning of the antigen injections. The other lavages were as for the other groups. BAL results on Day 1 were similar for each group. Cigarette smoking per se did not modify BAL in Group 3. EAA induction resulted in a large increase in all BAL cells, especially neutrophils of recovered fluid, which increased from 38 x 10(3) to 1,474 x 10(3) ml-1 (p less than 0.01) in Group 2 and from 58 x 10(3) to 740 x 10(3) in Group 3 (p less than 0.01). After maintenance, BAL neutrophils.ml-1 decreased to 444 x 10(3) in Group 2 (p less than 0.01), but stayed the same in Group 3: 973 x 10(3). After EAA induction, BAL neutrophils.ml-1 were higher in Group 2 than in Group 3 (p = 0.039); however, Group 2 had less neutrophils.ml-1 than Group 3 (p = 0.035) after EAA maintenance. We conclude that EAA results in a neutrophilic alveolitis and which can be evaluated by sequential BAL, and that cigarette smoking decreases the initial neutrophilic response and retards the eventual recovery during maintenance injections.     

Origin-specific DNA-binding membrane-associated protein may be involved in repression of initiation of DNA replication in Bacillus subtilis.

Previous binding studies with labeled double-stranded Bacillus subtilis DNA fragments to a protein blot of renatured Bacillus membrane proteins showed selective binding of two adjacent origin fragments to a 64-kDa protein. The selective binding of the 64-kDa protein could be blocked by prior incubation of the blots with a specific polyclonal antibody. An in vitro replication system derived from a B. subtilis DNA-membrane complex showed initiation activity without addition of exogenous enzymes or template. When the complex was first incubated with the 64-kDa antibody or with its Fab fragments, initiation activity was enhanced. Antibodies to several other Bacillus membrane proteins as well as nonspecific antibodies did not show any significant stimulatory effect. A heavy-density-label experiment indicated that the complex initiated multiple rounds of replication in the presence of the 64-kDa antibody but not in its absence. The 64-kDa antibody plus an initiation inhibitor (streptovaricin) showed only repair and elongation activity. The 64-kDa protein may act in vivo as a repressor/regulator of initiation activity.     

Diagnosis of human African trypanosomiasis and visceral leishmaniasis based on the detection of anti-parasite-enzyme antibodies

A sensitive diagnostic assay for parasitic infections based on the detection of anti-enzyme antibodies is presented. All serum antibodies produced in response to parasite antigens are immobilized via their Fc domain on matrix-bound protein G. Incubation of the immobilized antibodies with saturating amounts of parasite extract results in the binding of all recognized antigens, including those directed against a specific and readily measurable enzyme. The amount of bound enzyme is proportional to the anti-enzyme antibody concentration in the serum. The application of this principle is demonstrated for the diagnosis of both human African trypanosomiasis and visceral leishmaniasis by the detection of antibodies against parasite acid phosphatases.     

Assessment of mosquito larvicidal potency of cyclic lipopeptides produced by Bacillus subtilis strains

In this study, mosquito larvicidal potency of cyclic lipopeptides (CLPs) secreted by two Bacillus subtilis strains were determined. LC50 of the crude CLPs secreted by B. subtilis DM-03 and DM-04 strains against third instar larvae of Culex quinquefasciatus was 120.0+/-5.0 and 300.0+/-8.0mg/l respectively post 24 h of treatment. Physico-chemical factors such as pH of water, incubation temperature, heating and exposure to sunlight hardly influenced the larvicidal potency of these CLPs. Present study provided the evidence that B. subtilis lipopeptides were safe to Indian major carp Labeo rohita, a non-target aquatic organism. These properties of B. subtilis CLPs can be exploited for the formulation of a safer, novel biopesticide for effective control of mosquito larvae.     

Long-term results of prolonged treatment in patients with fibrosing alveolitis (prophylactic medical examination)

The results of a long-term (5-10 year) follow-up were studied in 109 patients with alveolitis, including 89 with EAA and 20 with IFA. A variety of treatments were applied. The predominant treatments were hormonal therapy supplemented by plasmapheresis, physiotherapy, oxygen therapy, etc. A follow-up of patients with alveolitis was made by 3 groups. Group 1 was compensated--Stage 0; Group 2, subcompensated--Stage II; Group 3, decompensated--Stage III. The control periods and scope of examinations were defined for each group. The Regulations governing the prophylactic medical examination of patients with alveolitis were worked out. Among patients with EAA, good results, such as improvement and stabilization of the process, were observed in 34.8% of cases, poor results, such as recurrences were in 53.6%, death rates were 3%. Among patients with IFA, good results were achieved in 15% of cases, recurrences and progression were in 10 and 30.7%, respectively, death rates were 40%.     

Involvement of eicosanoids and surfactant protein D in extrinsic allergic alveolitis.

The pathophysiology of extrinsic allergic alveolitis (EAA) involves oxidative lung damage as well as interstitial and alveolar inflammation. Macrophages and mast cells are inflammatory components of EAA that produce both leukotrienes (LTs) and prostaglandin D2 (PGD2). In addition, PGD2 is also produced by the free-radical-catalysed peroxidation of arachidonic acid during oxidative stress. Urinary 8-iso prostaglandin F2alpha (8-isoPGF2alpha) and serum surfactant protein D (SP-D) are considered appropriate biomarkers of oxidative stress and interstitial lung disease activity, respectively. The present study aimed to assess the association of these biomarkers with the pathophysiology of EAA. Two cases of acute EAA caused by the inhalation of fungi spores were reported. Eight asthmatic patients and six healthy control subjects were also enrolled in the current study. The serum SP-D and urinary eicosanoid (LTE4, PGD2 metabolite (9alpha,11betaPGF2), 8-isoPGF2alpha) concentrations markedly increased during the acute exacerbation phase. These concentrations decreased following corticosteroid therapy in the EAA patients. There was a significant correlation between serum SP-D and urinary 9alpha,11betaPGF2 concentrations in the EAA patients. In conclusion, although the present study proposes that serum surfactant protein-D and urinary eicosanoids are new biomarkers involved in the various immunological responses in extrinsic allergic alveolitis, further large-scale studies are needed to investigate the role of these compounds, not just as biomarkers, but also as biological potentiators of extrinsic allergic alveolitis.     

IgM-ELISA法早期诊断广州管圆线虫感染的初步研究

目的探索广州管圆线虫病IgM早期诊断时机。方法从感染福寿螺中分离第Ⅲ期幼虫,感染6w龄Balb/c小白鼠,分别于感染前及感染后的第1、2、3、4、8、16、21、28、38d取血。经方阵滴定确定最佳抗原包被量和血清最佳包被浓度,进一步测定感染广州管圆线虫小鼠的不同时期血清中IgM含量,同时设立阴性、阳性对照。结果小鼠血清中IgM抗体在感染后就开始升高,感染后第8dIgM抗体检测阳性率已达100%。结论感染后1w,小鼠血清中IgM检测已具有临床诊断价值。     

Human antibodies against spores of the genus Bacillus: a model study for detection of and protection against anthrax and the bioterrorist threat

A naive, human single-chain Fv (scFv) phage-display library was used in bio-panning against live, native spores of Bacillus subtilis IFO 3336 suspended in solution. A direct in vitro panning and enzyme-linked immunosorbent assay-based selection afforded a panel of nine scFv-phage clones of which two, 5B and 7E, were chosen for further study. These two clones differed in their relative specificity and affinity for spores of B. subtilis IFO 3336 vs. a panel of spores from 11 other Bacillus species/strains. A variety of enzyme-linked immunosorbent assay protocols indicated these scFv-phage clones recognized different spore epitopes. Notably, some spore epitopes markedly changed between the free and microtiter-plate immobilized state as revealed by antibody-phage binding. An additional library selection procedure also was examined by constructing a Fab chain-shuffled sublibrary from the nine positive clones and by using a subtractive panning strategy to remove crossreactivity with B. licheniformis 5A24. The Fab-phage clone 52 was improved compared with 5B and was comparable to 7E in binding B. subtilis IFO 3336 vs. B. licheniformis 5A24, yet showed a distinctive crossreactivity pattern with other spores. We also developed a method to directly detect individual spores by using fluorescently labeled antibody-phage. Finally, a variety of "powders" that might be used in deploying spores of B. anthracis were examined for antibody-phage binding. The strategies described provide a foundation to discover human antibodies specific for native spores of B. anthracis that can be developed as diagnostic and therapeutic reagents.     

Autoantibodies in paraneoplastic neurological syndrome

Paraneoplastic neurological syndrome is a rare disorder caused by the secondary effects of cancer and is thought to be immune-mediated. A high titer of autoantibodies in the patient's serum and cerebrospinal fluid, directed against both neurons and tumor, have been detected in some forms of this syndrome. These autoantibodies are considered the result of an immunological response to tumor and may cross-react with cells of the nervous system, causing neuronal damage. Specific forms of this syndrome are often associated with specific antineuronal antibodies and tumors. The onset of neurological symptoms and detection of these antibodies often precede the diagnosis of the tumor; therefore, detection of these antibodies greatly assists the diagnosis of this syndrome and prompts investigations for the underlying tumor. The pathogenicity of these antineuronal antibodies has been proven in only a few cases, such as that of anti-voltage gated calcium-channel antibodies in Lambert-Eaton myasthenic syndrome. The selective involvement of specific types of neurons has not been fully elucidated. The target spectrum of some of these antineuronal antibodies correlates well with the neurological symptoms, but that of others is wider than expected from the symptoms. Interesting evidence has suggested that these antionconeuronal antibodies can suppress tumor growth. The discovery of new antibodies and characterization of target molecules have been reported with advances in the field of molecular biology. A more detailed understanding of the relationship between the cancer and the neural involvement from the molecular biological standpoint may lead to rational tumor therapy and elucidation of the mechanism of neuronal death. Here, major clinical forms with well-known antineuronal antibodies and specific tumors are reviewed; for each antineuronal antibody, the target antigens and its putative role in the pathogenesis of this syndrome are described.