Eosinophil Clusters Research Articles

Non-ulcer Dyspepsia and Duodenal Eosinophilia: An Adult Endoscopic Population-Based Case-Control Study

Functional abnormalities of the duodenum have been observed in non-ulcer dyspepsia. We aimed to identify whether eosinophils in the upper gastrointestinal tract are a biomarker for non-ulcer dyspepsia. A random sample of an adult Swedish population (n = 1001; mean age, 54 y; 51% female) underwent upper endoscopy. Non-ulcer dyspepsia cases (n = 51, Rome II) and randomly selected controls (n = 48) were identified. Two blinded independent observers assessed the gastroduodenal eosinophil counts. Eosinophils were quantified by counting the number per 5 high-power fields at each of 5 sites (cardia, body, antrum, D1 duodenal bulb, and D2 second portion of duodenum), and total counts were summed over the 5 fields at each site. The odds ratio for non-ulcer dyspepsia (vs asymptomatic controls) in subjects with high duodenal bulb eosinophil counts (median, >/=22, relative to <22) was 11.7 (95% confidence interval, 3.9-34.9), adjusting for age, sex, and H pylori; similar results were observed in D2 (odds ratio = 7.3; 95% confidence interval, 2.9-18.1). A significant association with the number of eosinophil clusters was detected in the duodenum, with higher values in non-ulcer dyspepsia (P < .01). By immunostaining with major basic protein antibody in a subset of duodenal biopsy specimens, eosinophil degranulation was observed in non-ulcer dyspepsia (7 of 15 vs 0 of 5 controls; P = .11). Gastric eosinophil counts were overall not significantly increased in non-ulcer dyspepsia vs controls. Early satiety was associated with eosinophilia in D1 (P = .01) and D2 (P = .02), adjusting for age, sex, and H pylori. Duodenal eosinophilia may characterize a subset of adults with non-ulcer dyspepsia.

The role of fungi in the etiology of chronic rhinosinusitis: A prospective study

Objectives Allergic fungal sinusitis (AFS) may represent an endpoint in a spectrum of sinonasal disease. Patients fulfilling criteria for a diagnosis of AFS have a poor prognosis often requiring multiple surgeries. The detection of ‘allergic mucin’ with mucus containing clusters of eosinophils and the detection of fungi by histological examination or culture is key criteria necessary for diagnosis. This study was performed to assess the strength of the association of the presence of fungi with the presence of eosinophils in a group of patients with chronic rhinosinusitis and controls. Methods Thirty patients with a clinical diagnosis of chronic rhinosinusitis and 10 individuals as control group were selected for the study. Total serum IgE level testing, nasal mucus cytology and fungal culture were performed in all subjects. Results Fungal spores were present in the nasal mucus in 14 patients with rhinosinusitis, and in 7 controls. The detection of eosinophils on cytology correlated significantly both with a clinical diagnosis of chronic rhinosinusitis (95% confidence intervals (CI) 0.34–0.81) and with the presence of fungal elements on cytology ( p = 0.02). The average serum IgE level was higher in patients with fungal spores ( p = 0.039). Conclusion In certain susceptible individuals inhaled fungi may provoke an eosinophilic response. This response varies from simple eosinophilic inflammation to classic allergic fungal sinusitis.

Advances in upper airway diseases and allergen immunotherapy

The purpose of this review is to highlight important articles on upper airway disease and immunotherapy that appeared in the Journal of Allergy and Clinical Immunology and elsewhere during 2005. In recent studies of tissue from patients with chronic hypertrophic eosinophilic sinusitis, increased leukotriene C4 synthase and 5-lipoxygenase activity and increased levels of cysteinyl leukotriene production were demonstrated that correlated with disease severity but not with whether the patient was aspirin sensitive. However, the cysteinyl leukotriene 1 receptor was increased in leukocytes in the sinus tissue only in those patients with aspirin sensitivity. Major basic protein, released by eosinophils into the mucus in the paranasal sinus lumen, was found to reach concentrations capable of damaging the sinus epithelium, predisposing to bacterial infections. Testing the hypothesis that chronic hypertrophic eosinophilic sinusitis represents a reaction to common fungi, a double-blind trial of intranasal instillation of amphotericin B was conducted. There were marginal but significant differences in favor of amphotericin B treatment for sinus mucosal thickening on the basis of computed tomography and the evidence of eosinophilic inflammation in the sinus mucus. The effectiveness of topical nasal corticosteroids for treatment of nasal polyps was confirmed in 2 large studies. Improvement in sleep quality and daytime drowsiness in patients with allergic rhinitis treated with nasal corticosteroids was reported to correlate with reduction in nasal obstruction. The statistical analysis behind studies that reported a decrease in asthma exacerbations with nasal corticosteroids or oral antihistamines has been questioned. It appears that the results of at least one of these studies are indeed too good to be true. Although caution is still indicated in administering immunotherapy to patients receiving beta-adrenergic blocking agents, the prohibition might not be absolute. A study in patients with Hymenoptera sensitivity given venom immunotherapy revealed no increase in serious adverse reactions to venom injections and no greater incidence of reactions to insect stings in those taking beta-blocking agents. Sublingual immunotherapy for 8 to 12 weeks in patients with hazelnut sensitivity significantly increased their tolerance to hazelnut in double-blind, placebo-controlled challenges while inducing increased IgG4 and IL-10 levels, indicating induction of regulatory T cells. There were a number of articles in the Journal of Allergy and Clinical Immunology in 2005 that addressed the entity of chronic hypertrophic eosinophilic sinusitis. In addition, an update of the "Practice parameters on sinusitis" was published. The major focus in allergen immunotherapy continues to be sublingual administration.

Concomitant Histopathological Findings of Allergic Fungal Sinusitis and Fungal Ball in the Same Sinus: A Rare Case Report

BACKGROUND: Allergic fungal sinusitis (AFS) and fungal ball (mycetoma) are two forms of noninvasive fungal sinusitis distinct in their clinical presentations, histopathologic features, treatment modalities, and prognoses. We report an unusual case where histopathological findings of both entities were found in the same sinus. CASE: A 63-year-old immunocompetent man with a history of allergic rhinitis, asthma and chronic rhinosinusitis (CRS) was referred to our clinic for worsening of asthma and sinonasal symptoms one year after undergoing maxillary sinus surgery. Laboratory investigations revealed peripheral eosinophilia (1300/μL) and a markedly elevated total IgE level (5469 kU/L; normal value <165 kU/L). Skin prick test was positive to A. fumigatus. The possibility of allergic bronchopulmonary aspergillosis was excluded with a normal CT of the chest. Sinus CT showed extensive mucosal changes of CRS; additionally, there was opacification associated with areas of calcification in the right maxillary sinus. At endoscopic sinus surgery, a large fungal ball embedded in thick mucus was recovered from the sinus. GMS staining showed dense branching fungal hyphae within the fungal mass and rare hyphal elements within the mucus. H&E staining revealed abundant clusters of eosinophils, consistent with allergic mucin. Mucosal biopsy demonstrated eosinophilic inflammation without fungal invasion. Cultures were negative. Systemic and topical steroids were initiated to reduce the eosinophilic inflammatory response and prevent disease recurrence. CONCLUSIONS: This is an unusual case of AFS and fungal ball coexistence in the same sinus, illustrating the importance of considering AFS as a diagnostic possibility in the presence of chronic rhinosinusitis associated with IgE-mediated hypersensitivity to fungi.

Striking deposition of toxic eosinophil major basic protein in mucus: Implications for chronic rhinosinusitis

The mechanisms by which eosinophilic inflammation damages the epithelium and contributes to recurrent acute exacerbations in chronic rhinosinusitis (CRS) have not been fully elucidated. We tested the hypotheses that eosinophils deposit toxic major basic protein (MBP) in the mucus and that MBP reaches concentrations able to damage the sinonasal epithelium. Tissue specimens with mucus attached to the tissue were carefully collected from 22 patients with CRS and examined by using immunofluorescence staining for MBP. This immunofluorescence was digitally analyzed to determine the area covered by MBP and the intensity of the staining (estimating MBP concentration). Levels of MBP in extracts from nasal mucus were quantitated by means of RIA. Heterogeneous eosinophilia was evident within tissue and mucus specimens. All tissue specimens showed intact eosinophils, but diffuse extracellular MBP deposition, as a marker of eosinophil degranulation, was rare. In contrast, all mucus specimens showed diffuse MBP throughout and abundant diffuse extracellular MBP deposition within clusters of eosinophils. Digitized analyses of MBP immunofluorescence revealed increased area coverage (P < .0001) in mucus compared with that seen in tissue. Estimated concentrations of MBP within the clusters suggested toxic levels. MBP concentrations in mucus extract reached 11.7 microg/mL; MBP was not detectable in healthy control subjects. In patients with CRS, eosinophils form clusters in the mucus where they release MBP, which is diffusely deposited on the epithelium, a process not observed in the tissue. Estimated MBP levels far exceed those needed to damage epithelium from the luminal side and could predispose patients with CRS to secondary bacterial infections.

Eosinophilic esophagitis in children: symptoms, histology and pH probe results.

To review the authors' experience with eosinophilic esophagitis. Between 1993 and 2001, the authors identified 12 patients with eosinophilic esophagitis defined on histologic criteria (> or = 20 eosinophils per high-power field in the distal esophageal epithelium). The authors reviewed medical records for details of clinical presentation; laboratory data; radiologic, endoscopic, and histologic findings; and the results of continuous esophageal pH probe monitoring. Seventy-five percent of the patients were male. The median age at presentation was 10.8 years (range, 1-17 years). Commonly reported symptoms were dysphagia with solid food (66%), epigastric pain (42%), food impaction (50%), and vomiting (8%). Food allergy was reported in 50% and asthma in 33%. Peripheral eosinophilia (> 700/mm3) was found in 42%. Upper gastrointestinal series performed in eight patients, showed esophageal luminal narrowing in three. Computed tomography, performed in two patients, revealed thickening of the esophageal wall. Esophageal pH probe monitoring, performed in nine patients, revealed no abnormal acid reflux. All of the monitored patients had episodic alkalinization of the esophagus. Upper endoscopic analysis revealed white specks on the esophageal mucosa in 42%, esophageal narrowing in 33%, esophageal rings in 25%, and esophageal furrowing in 8%. The mean eosinophils per high-power field was 65 (range, 20-200). Histologic characteristics included juxtaluminar (33%) and peripapillary clusters of eosinophils (33%), increased papillary height (50%), and basal cell hyperplasia (34%). Solid food dysphagia was the most common feature of eosinophilic esophagitis in our patients. Alkalinization of the esophagus was found in all nine pH probe recordings of eosinophilic esophagitis patients and may represent a previously unreported characteristic of the condition.

Eosinophilic Esophagitis in Children: Symptoms, Histology and pH Probe Results

ABSTRACTAim:To review the authors’ experience with eosinophilic esophagitis.Methods:Between 1993 and 2001, the authors identified 12 patients with eosinophilic esophagitis defined on histologic criteria (≥20 eosinophils per high‐power field in the distal esophageal epithelium). The authors reviewed medical records for details of clinical presentation; laboratory data; radiologic, endoscopic, and histologic findings; and the results of continuous esophageal pH probe monitoring.Results:Seventy‐five percent of the patients were male. The median age at presentation was 10.8 years (range, 1–17 years). Commonly reported symptoms were dysphagia with solid food (66%), epigastric pain (42%), food impaction (50%), and vomiting (8%). Food allergy was reported in 50% and asthma in 33%. Peripheral eosinophilia (&gt;700/mm3) was found in 42%. Upper gastrointestinal series performed in eight patients, showed esophageal luminal narrowing in three. Computed tomography, performed in two patients, revealed thickening of the esophageal wall. Esophageal pH probe monitoring, performed in nine patients, revealed no abnormal acid reflux. All of the monitored patients had episodic alkalinization of the esophagus. Upper endoscopic analysis revealed white specks on the esophageal mucosa in 42%, esophageal narrowing in 33%, esophageal rings in 25%, and esophageal furrowing in 8%. The mean eosinophils per high‐power field was 65 (range, 20–200). Histologic characteristics included juxtaluminar (33%) and peripapillary clusters of eosinophils (33%), increased papillary height (50%), and basal cell hyperplasia (34%).Conclusion:Solid food dysphagia was the most common feature of eosinophilic esophagitis in our patients. Alkalinization of the esophagus was found in all nine pH probe recordings of eosinophilic esophagitis patients and may represent a previously unreported characteristic of the condition.

'Eosinophilic fungal rhinosinusitis': a common disorder in Europe?

The traditional criteria for the diagnosis of allergic fungal sinusitis include chronic rhinosinusitis, "allergic mucin" (mucus containing clusters of eosinophils), and detection of fungi by means of histological examination or culture. In 1999, a group of Mayo Clinic researchers, with a novel method of mucus collection and fungal culturing technique, were able to find fungi in 96% of patients with chronic rhinosinusitis. Immunoglobulin E-mediated hypersensitivity to fungal allergens was not evident in the majority of their patients. Because the presence of eosinophils in the allergic mucin, not a type I hypersensitivity, is probably the common denominator in the pathophysiology of allergic fungal sinusitis, the Mayo Clinic group proposed a change in terminology from allergic fungal sinusitis to eosinophilic fungal rhinosinusitis. Using new techniques of culturing fungi from nasal secretion, as well as preservation and histological examination of mucus, we investigated the incidence of "eosinophilic fungal rhinosinusitis" in our patient population. STUDY DESIGN METHODS: In an open prospective study nasal mucus from patients with chronic rhinosinusitis as well as from healthy volunteers was cultured for fungi. In patients, who underwent functional endoscopic sinus surgery, nasal mucus was investigated histologically to detect fungi and eosinophils within the mucus. Fungal cultures were positive in 84 of 92 patients with chronic rhinosinusitis (91.3%). In all, 290 positive cultures grew 33 different genera, with 3.2 species per patient, on average. Fungal cultures from a control group of healthy volunteers yielded positive results in 21 of 23 (91.3%). Histologically, fungal elements were found in 28 of 37 patients (75.5%) and eosinophilic mucin in 35 of 37 patients (94.6%). Neither fungi nor eosinophils were present in 2 of 37 patients (5.4%). Our data show that the postulated criteria of allergic fungal sinusitis are present in the majority of patients with chronic rhinosinusitis. Either those criteria will be found to be invalid and need to be changed or, indeed, "eosinophilic fungal rhinosinusitis" exists in the majority of patients with chronic rhinosinusitis. Based on our results, fungi and eosinophilic mucin appear to be a standard component of nasal mucus in patients with chronic rhinosinusitis.

Incidence and detection of fungi and eosinophilic granulocytes in chronic rhinosinusitis

Chronic Rhinosinusitis (CRS) is the most common chronic disease in the United States. Though for Europe no data are available, we have to assume that the situation is similar. Although the disease is defined very well by clinical symptoms, up to date the etiology and pathogenesis of chronic rhinosinusitis are unknown. CRS is considered to be multifactorial, with thickening of the mucosa and formation of polyps as an end stage of the disease. Treatment of choice includes corticosteroids and/or endoscopic or microscopic surgery. Antibiotics only help, if there is an acute bacterial exacerbation of the disease. They are not able to cure chronic rhinosinusitis per se. In 1999 Mayo Clinic researchers published data concerning the incidence of so-called "allergic" fungal sinusitis (AFS) in their patients suffering from chronic rhinosinusitis, demonstrating the majority of patients investigated presenting those criteria. Our own initial data from 2000 confirmed their findings. In an open prospective study fungal cultures were obtained from nasal mucus of 238 consecutive patients suffering from CRS. As control group acted 23 members of our staff, who did not show any evidence for CRS. In addition, in 37 CRS patients surgical specimens (mucus and tissue) were investigated histologically for evidence of eosinophilic granulocytes and fungal elements. Using new techniques for fungal detection in culture and histology as proposed by Mayo Clinic researchers, positive detection of fungal cultures of the mucus of our CRS patients developed from 7 % in the past up to 87 % at present. 91.3 % of our control group yielded a positive result in fungal culture. Histologically, eosinophilic clusters were evident in 94.6 % and fungal elements were detected in 75.5 % within the mucus of 37 surgical CRS patients. Overall, 89.2 % of our surgical patients thus fulfilled the criteria of so-called AFS. Compared to our findings in the past, our latest results show an increase of 80 % in detection of fungal elements in our CRS patients. In all we were able to identify 654 positive fungal cultures in 238 CRS patients and 23 healthy controls respectively. 88 different genera grew, with 2.4 different species per patient and 3.1 different species per healthy control, on average. Utilizing new techniques of fungal culturing out of the mucus of CRS patients and healthy controls, the number of positive fungal cultures increased dramatically from 7 % to 87 % in our patients and 91.3 % in healthy controls respectively. To obtain these results it is crucial to perform special techniques of mucus sampling and pretreatment for culturing as well as for histological investigations. Our results show, that with suitable techniques fungi can be identified in almost everybody's nose, CRS patient or healthy. When inhaled, those airborne fungi are only "in transit" through the nose. Positive fungal cultures from nasal secretion therefore have to be considered normal findings. The reason for this delayed recognition has to be attributed to our inadequate methods in the past. In contrast to healthy controls, clusters of eosinophils and fungal elements are present simultaneously within the mucus of CRS patients and appear to be a marker of the disease.

Structural brain aging in inbred mice: potential for genetic linkage.

To identify genetic factors involved in brain aging, we have initiated studies assessing behavioral and structural changes with aging among inbred mouse strains. Cognitive performance of C57BL/6J mice is largely maintained with aging, and stereological analysis revealed no significant age-related change in neuron number, synaptic bouton number or glial number in the hippocampus. Moreover, no change in cortical neuron number and cholinergic basal forebrain neuron number has been found in this strain. 129Sv/J mice have more pronounced age-related cognitive deficits, although hippocampal and basal cholinergic forebrain neuron number also appear unchanged with aging. Differences in neurogenesis and neuron vulnerability in the adult CNS of C57BL/6, 129/Sv and other inbred strains have been reported, which in turn may have important consequences for brain aging. Age-related lesions, such as thalamic eosinophilic inclusions and hippocampal clusters of polyglucosan bodies also vary greatly among inbred strains although the functional significance of these lesions is not clear. The continued assessment of such age-related structural and behavioral changes among inbred mouse strains offers the potential to identify genes that control age-related changes in brain structure and function.

Epithelial Damage of Nasal Mucosa in Nasal Allergy

Epithelial alterations arising from moderate nasal allergy to house dust were examined and compared to findings in epithelia from nonallergic controls. Biopsy specimens were taken during natural allergen exposure from two different sites: 1) the anterior tip of the inferior turbinate and 2) 2 cm behind it. The tissues were examined by both electron and light microscopy. In the allergic group, epithelial damage was found to be remarkable in the anterior nasal mucosae, where nonciliated cells were prevalent, but minor in the posterior nasal mucosae comprising ciliated and goblet cells. In the anterior nasal mucosae, conspicuous intercellular edema, epithelial shedding, and clusters of eosinophils in the epithelial layer were observed, whereas only a little epithelial shedding and edema in the basal area of the epithelium was noted in the ciliated areas. In controls, pathologic changes were not observed, although a little epithelial shedding was seen in the anterior turbinate. Although there are arguments for and against epithelial shedding in nasal allergy, this study confirms its presence even in patients with moderate allergy.

Increased proliferation of eosinophil clusters in myelodysplastic syndromes

A patient with myelodysplastic syndromes (MDS) developed eosinophilia during treatment with recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). To study the mechanism of this eosinophilia, we investigated the proliferation of eosinophil colony-forming units (CFU-Eo) in nine patients and four healthy controls. Eosinophil clusters increased significantly in the patients ( P < 0.01) compared with controls, but eosinophil colonies were not different between controls and MDS patients. In addition, the eosinophil clusters were significantly increased with rhGM-CSF in MDS patients compared with controls, although serum GM-CSF concentrations were similar in both groups. These results suggest that eosinophil clusters are increased in MDS either through abnormal progenitor proliferation or hypersensitivity to GM-CSF.

Peculiar axonal debris with subsequent astrocytic response (foamy spheroid body). A topographic, light microscopic, immunohistochemical and electron microscopic study.

Foamy spheroid bodies (FSBs) are described, as newly identified pathological structures occurring in human brain. FSBs favoured the substantia nigra pars reticulata (SNPR) and/or globus pallidus (GP) in degenerative conditions especially postencephalitic parkinsonism, progressive supranuclear palsy, pallido-nigro-luysial atrophy and multiple system atrophy. No FSBs were observed anywhere in the presence of substantia nigra pars compacta (SNPC) degeneration, such as occurs in idiopathic Parkinson's disease, or luysio-pallidal system degeneration, such as found in dentato-rubro-pallido-luysial atrophy or Joseph's disease. FSBs were also occasionally identified in the substantia nigra (SN) and/or GP of aged persons. In addition to SN and GP lesions, FSBs were seen in diffuse axonal lesions of long fibre tracts (the corpus callosum, the superior cerebellar peduncle) after non-missile head injuries, and in peri-infarct lesions. Under the light microscope, FSBs appear as slightly eosinophilic, foamy and nearly round objects with vague outlines, measuring approximately 10-50 microns in diameter. Some FSBs contain coarse, eosinophilic clusters at their periphery. FSB stained black when stained by the Gallyas silver method. Some FSBs were immunohistochemically positive for synaptophysin and 68 kDa neurofilament. Glial fibrillary acidic protein-positive fibres were observed alongside and/or inside some FSBs. Electron microscopically, FSBs were found to consist of collections of neuritic debris containing a variety of dense bodies and a small number of both mitochondria and neurofilaments. Some such collections were surrounded by astrocytic processes. These findings strongly suggest that FSBs are collections of small axonal debris destined for removal by astrocytes in due course. A variety of factors (degeneration of the SNPR and/or the GP, injury, infarction, ageing) seemed to be responsible for the histogenesis of FSBs.

Comparative analysis of the influences of human gamma, alpha and beta interferons on human multipotential (CFU-GEMM), erythroid (BFU-E) and granulocyte-macrophage (CFU-GM) progenitor cells.

Preparations of human interferon (HuIFN) immune (gamma) (2 X 10(7) units/mg protein), HuIFN leukocyte (alpha) (1.4 X 10(8) units/mg protein) and HuIFN fibroblasts (beta) (10(6) U/mg protein) were assessed for their influence on colony formation of human hematopoietic progenitor cells: colony forming unit-granulocyte, erythroid, macrophage, megakaryocyte (CFU-GEMM), burst forming unit-erythroid (BFU-E), day 7 colony forming unit granulocyte-macrophage (CFU-GM) and day 14 CFU-GM. Colony formation by CFU-GEMM and BFU-E was suppressed equally by the three preparations of HuIFN, but colony formation by CFU-GM was suppressed differentially. CFU-GM were, on the whole, more responsive to HuIFN gamma than HuIFN alpha, and HuIFN beta was least effective. HuIFN alpha, but not HuIFN gamma or HuIFN beta, suppressed colony formation from CFU-GM without also suppressing the total number of colonies plus clusters. This was due to an increase in the numbers of clusters formed in the presence of HuIFN alpha. The suppressive influence on colonies from CFU-GM by the preparations of HuIFN and the enhancement of clusters by HuIFN alpha was apparently equal for colonies and clusters of neutrophils, eosinophils, macrophages and neutrophils plus macrophages. The suppressive effects of HuIFN gamma were inactivated by a monoclonal antibody to HuIFN gamma and the suppressive and enhancing effects of HuIFN alpha were inactivated with a heteroantiserum to HuIFN alpha. Depletion of monocytes, T lymphocytes and B lymphocytes from the target bone marrow cells had no influence on the effects of the preparations of HuIFN. These results demonstrate that the effects of HuIFN gamma and HuIFN alpha are due to the HuIFN themselves and that these actions on the hematopoietic progenitor cells are probably not mediated through monocytes and/or lymphocytes.

The structure of bronchial plugs in mucoid impaction, bronchocentric granulomatosis and asthma.

The structure of bronchial plugs was examined in 12 lobectomy specimens from patients with bronchocentric granulomatosis and mucoid impaction, two bronchial biopsies from patients with mucoid impaction, sections from one post-mortem showing evidence of mucoid impaction and bronchocentric granulomatosis as well as aspergilloma with tissue invasion and from post-mortems on eight patients who had died during a persisting exacerbation of their asthma. In both mucoid impaction and asthma eosinophils were arranged in layers within the mucus, but the pattern of lamination was different in the two groups. In asthma the layers of eosinophils appeared as whorls and eddies. In mucoid impaction the lamination was parallel to the circumference of the plug and the eosinophils were tightly compacted and appeared degenerate; fungal elements were found in all cases and were more readily seen among the eosinophils than in the mucus. The histological appearance of even small fragments of such plugs is diagnostic of allergic bronchopulmonary fungal disease with mucoid impaction. In all our cases bronchocentric granulomatosis appears to have been a complication of allergic bronchopulmonary aspergillosis with mucoid impaction. The clusters of inspissated eosinophils so typical of the peripheral lesion of bronchocentric granulomatosis appear to be fragments of the mucus plugs formed in the larger bronchi.