Japanese guidelines for occupational allergic diseases 2017.

In 2013, a guideline for occupational allergic diseases was published for the first time in Japan. Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative antigens, and are socioeconomically important diseases with which the patients might sometimes lose jobs due to work interruptions. Guidelines for occupational allergic diseases have been published in many countries. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis and occupational anaphylaxis shock, and legal aspects of these diseases. The guideline is characterized with the following basic structure: Clinical Questions (CQs) are set with reference to Minds (Medical Information Network Distribution Service), statements by the committee are correspondingly listed, recommended grades and evidence levels are defined, and then descriptions and references are indicated.

Effective allergen avoidance for reducing exposure to house dust mite allergens and improving disease management in adult atopic asthmatics.

OBJECTIVE: We investigated the best strategy for adult asthmatics to avoid exposure to Dermatophagoides group (Der-1) allergens. METHODS: Adult atopic asthmatics (n = 111) followed a 32-item checklist for avoiding Der-1 allergen exposure. Twenty-five patients were excluded through incomplete sampling; 50 remaining patients encased their pillows/futons/mattresses in microfine-fiber covers, 13 used vacuum cleaners with dust-mite-collection nozzles, and 23 acted as non-intervention controls. During August-October 2010 and August-October 2011, dust samples were collected in Petri dishes placed in bedrooms for 2 weeks and from mattresses/futons by using adhesive tape on one morning. A Der-1 level decrease was defined as a mean 2011 Der-1 level of <1 as a ratio of the 2010 level on tape or Petri dish samples. We analyzed the associations between Der-1 level change (by ELISA) and % weekly variability in peak expiratory flow (PEF) or fraction of exhaled nitric oxide (FeNO) after intervention. RESULTS: Der-1 levels decreased significantly in the covers group but not the vacuuming group. FeNO levels and PEF variability were unchanged in both groups. In patients whose Petri dish or tape samples showed decreased Der-1 levels, the % PEF variability was lower in 2011 than in 2010, but FeNO levels were unchanged. Three interventions (vacuuming all family members' mattress/futon surfaces at least weekly or after exposure of the futons to sunlight, and floor wiping before vacuuming), plus using covers, were the most effective management strategy in reducing Der-1 levels. CONCLUSIONS: This environmental and bedding maintenance program may help manage adult atopic asthma.

Platelet activation markers overexpressed specifically in patients with aspirin-exacerbated respiratory disease.

BACKGROUND: Aspirin-exacerbated respiratory disease (AERD) is characterized by respiratory reactions on ingestion of COX-1 inhibitors and cysteinyl leukotriene overproduction. The hypersensitivity reaction is induced by low doses of aspirin that inhibit COX-1 in platelets. OBJECTIVE: We sought to explore the role of platelets in the pathogenesis of AERD in patients under stable conditions and during an aspirin challenge test. METHODS: Stable patients with AERD (n = 30), aspirin-tolerant asthma (ATA; n = 21), or idiopathic chronic eosinophilic pneumonia (n = 10) were enrolled. Platelet activation was estimated based on expression levels of P-selectin (CD62P), CD63, CD69, and GPIIb/IIIa (PAC-1) in peripheral platelets; percentages of circulating platelet-adherent leukocytes; and plasma levels of soluble P-selectin (sP-selectin) and soluble CD40 ligand (sCD40L). RESULTS: In the stable condition, expression of all surface markers on platelets, the percentage of platelet-adherent eosinophils, and the plasma levels of sP-selectin and sCD40L were significantly higher in patients with AERD compared with those in patients with ATA. P-selectin and CD63 expression on platelets and plasma sP-selectin and sCD40L levels were positively correlated with the percentage of platelet-adherent eosinophils. Among these markers, P-selectin expression and plasma sP-selectin levels positively correlated with urinary concentrations of leukotriene E4. Additionally, plasma sP-selectin and sCD40L levels were negatively correlated with lung function. In contrast, platelet activation markers in patients with AERD did not change during the aspirin challenge test. CONCLUSION: Peripheral platelets were activated more in patients with stable AERD compared with those in patients with stable ATA, patients with idiopathic chronic eosinophilic pneumonia, and control subjects. Platelet activation was involved in cysteinyl leukotriene overproduction and persistent airflow limitations in patients with AERD.

IgE Abs to Der p 1 and Der p 2 as diagnostic markers of house dust mite allergy as defined by a bronchoprovocation test.

BACKGROUND: Limited information is available regarding the clinical usefulness of measuring the levels of IgE to allergen components from house dust mites (HDMs) in the diagnosis of genuine HDM allergy. METHODS: To evaluate the diagnostic usefulness of measuring levels of serum IgE antibodies (Abs) to allergen components from Dermatophagoides pteronyssinus (DP) as a predictor of immediate asthmatic response (IAR) to bronchoprovocation, we studied 55 DP-sensitized asthmatic patients who underwent a bronchoprovocation test using crude DP extract. The levels of IgE Abs to crude DP, nDer p 1, rDer p 2, and rDer p 10 in patients who showed IAR (n = 41) were compared with those in patients who showed no IAR (n = 14). RESULTS: While the frequencies of positivity for IgE Abs to nDer p 1 and rDer p 2 among the entire study population were 89 and 86%, respectively, all patients with IAR tested positive for both of them with high IgE concentrations. The areas under the receiver operating characteristic curves for IgE to nDer p 1 and rDer p 2 as predictors of IAR were 0.913 and 0.906, respectively. The specificity of IgE to nDer p 1 and rDer p 2 was higher than IgE to crude DP even at low cut-off points. CONCLUSIONS: IgE to nDer p 1 and/or rDer p 2 was highly predictive of allergen-induced IAR. These findings validate the clinical usefulness of measuring the levels of IgE to nDer p 1 and rDer p 2 as a diagnostic tool for genuine HDM allergy.

Intravenous immunoglobulin for chronic residual peripheral neuropathy in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome): a multicenter, double-blind trial.

Eosinophilic granulomatosis with polyangiitis (EGPA), previously called Churg-Strauss syndrome, frequently affects the peripheral nervous system. We conducted a multicenter, double-blind, three-arm treatment period, randomized, pre-post trial to assess the efficacy of intravenous immunoglobulin (IVIg) administration for residual peripheral neuropathy in patients with EGPA that is in remission, indicated by laboratory indices. Twenty-three patients were randomly assigned into three groups, in which the timing of IVIg and placebo administration was different. Each group received one course of intervention and two courses of placebo at 2-week intervals. Treatment effects were assessed every 2 weeks for 8 weeks. The primary outcome measure, the amount of change in the manual muscle testing sum score 2 weeks after IVIg administration, significantly increased (p = 0.002). The results over time suggested that this effect continued until the last assessment was done 8 weeks later. The number of muscles with manual muscle testing scores of three or less (p = 0.004) and the neuropathic pain scores represented by the visual analogue scale (p = 0.005) also improved significantly 2 weeks after IVIg administration. This study indicates that IVIg treatment for EGPA patients with residual peripheral neuropathy should be considered even when laboratory indices suggest remission of the disease.

Occupational asthma from exposure to rye flour in a Japanese baker.

Three years after beginning employment at a bakery, a 32-year-old Japanese man began experiencing acute asthma exacerbations after exposure to rye flour. Antigen-specific serum IgE antibodies were detected to the albumin and globulin, gliadin, prolamin, and glutenin protein fractions of rye flour purified from the crude antigen, but only to the albumin and globulin fraction of wheat flour. The histamine concentration producing one-half maximal effect was lower for all four rye flour fractions than for the wheat flour fractions. After inhalation of the albumin and globulin fraction of rye flour, forced expiratory volume in 1 sec decreased to 77.7% of that pre-provocation. To our knowledge, this is the first report of baker's asthma due to rye flour in Japan.

An increase of CD83+ dendritic cells ex vivo correlates with increased regulatory T cells in patients with active eosinophilic granulomatosis and polyangiitis.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare disease characterized by the presence of allergic granulomatosis and necrotizing vasculitis with eosinophilic infiltration. The etiology of EGPA is unknown. Dendritic cells (DCs) are not only critical for the induction of primary immune responses; they may also be important for the induction of immunological tolerance and the regulation of the type of T-cell-mediated immune response. To investigate whether DC maturation is associated with EGPA disease status, we examined the relationship between the maturation of DCs and the differentiation of regulatory T (Treg) cells in EGPA patients. We exposed the CD14+ blood monocytes of 19 patients with EGPA in remission or relapse to stimulation with GM-CSF and IL-4 for 6 d and lipopolysaccharide for 24 h to obtain mature CD83+ DCs and immature CD206+ DCs. Using immunohistochemistry, we examined four patients for the presence of CD83+ and CD206+ DCs in the lung at the onset of EGPA. RESULTS: The percentage of CD83+ cells among DCs differentiated from CD14+ monocytes was lower for EGPA patients in relapse than in remission. The percentage of CD83+ DCs was inversely correlated with the percentage of CD206+ DCs and was significantly correlated with the numbers of naturally occurring CD4+ regulatory Treg (nTreg; FOXP3+CD4+) cells and inducible Treg (iTreg; CD4+CD25+ T cells producing IL-10 or TGF-ß) cells but not the number of eosinophils. The percentage of CD206+ DCs was significantly inversely correlated with the percentages of nTreg and iTreg cells but not the number of eosinophils. Immunohistochemistry revealed both CD206+ DCs and CD83+ DCs in alveoli and interstitial spaces at the onset of EGPA. CONCLUSION: The maturation of DCs from monocytes was related to disease activity in patients with EGPA. Increased CD83+ DCs in EGPA patients may induce the differentiation of iTreg and nTreg cells, thereby suppressing inflammation and disease activity.

Japanese Guideline for Occupational Allergic Diseases 2014.

In 2013, a guideline for occupational allergic diseases was published for the first time in Japan. Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative antigens, and are socioeconomically important diseases with which the patients might sometimes lose jobs due to work interruptions. Guidelines for occupational allergic diseases have been published in many countries. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis and occupational anaphylaxis shock, and legal aspects of these diseases. The guideline is characterized with the following basic structure: Clinical Questions (CQs) are set with reference to Minds (Medical Information Network Distribution Service), statements by the committee are correspondingly listed, recommended grades and evidence levels are defined, and then descriptions and references are indicated.

High-dose intravenous immunoglobulin therapy for eosinophilic granulomatosis with polyangiitis.

BACKGROUND: Regulatory T (Treg) cells are implicated in the development and progression of eosinophilic granulomatosis with polyangiitis (EGPA). We previously showed beneficial effects of intravenous immunoglobulin (IVIG) therapy combined with corticosteroid and immunosuppressant treatment on clinical symptoms, including mononeuritis multiplex and cardiac dysfunction, and Treg cell frequency, during EGPA. Whether the timing of administration (during initial treatment or at relapse after remission) or previous treatment affects the clinical and immunologic efficacy of IVIG is unknown. We evaluated whether the frequency of Treg cells varied depending on when IVIG was provided relative to the start of conventional therapy for EGPA. METHODS: The patient population for this retrospective analysis comprised 17 patients with severe mononeuritis multiplex or heart failure whose EGPA did not respond to corticosteroids combined with immunosuppressant therapy. Ten patients first received IVIG during initial treatment, whereas the remaining 7 patients first received IVIG on relapse after remission. We measured the percentage of Treg cells, defined as FOXP3(+)CD4(+) T cells, present before the first round of IVIG and at 1 month after the last IVIG treatment. RESULTS: FOXP3(+)CD4(+) T cells were increased in patients who required only a single course of IVIG to achieve remission compared with those who needed two or more courses. The dosage of prednisolone at initial IVIG was inversely correlated with the ratio of the number of FOXP3(+)CD4(+) T cells before IVIG and that at 1 month thereafter. CONCLUSION: Patients with severe EGPA who receive IVIG after nonresponse to high-dose prednisolone during initial treatment may need multiple courses of IVIG to achieve remission. An increase in the frequency of Treg cells after IVIG may predict the need for additional IVIG in EGPA.

Japanese Guideline for Occupational Allergic Diseases 2014.

In 2013, a guideline for occupational allergic diseases was published for the first time in Japan. Occupational allergic diseases are likely to worsen or become intractable as a result of continuous exposure to high concentrations of causative antigens, and are socioeconomically important diseases with which the patients might sometimes lose jobs due to work interruptions. Guidelines for occupational allergic diseases have been published in many countries. This guideline consists of six chapters about occupational asthma, occupational allergic rhinitis, occupational skin diseases, hypersensitivity pneumonitis and occupational anaphylaxis shock, and legal aspects of these diseases. The guideline is characterized with the following basic structure: Clinical Questions (CQs) are set with reference to Minds (Medical Information Network Distribution Service), statements by the committee are correspondingly listed, recommended grades and evidence levels are defined, and then descriptions and references are indicated.

Age-specific characteristics of inpatients with severe asthma exacerbation.

BACKGROUND: The characteristics of inpatients with severe asthma exacerbation remain unclear. It is considered that the characteristics of inpatients with severe asthma vary depending on age. However, these are rarely investigated. The objective of this study is to investigate the differences in characteristics among different age groups. We considered that it is necessary to understand the characteristics of each age group so that we can establish strategies in preventing severe asthma exacerbation. METHODS: All asthma inpatients who were hospitalized between 2004 and 2011 with SpO2 <90% (in room air), were breathless at rest, and showed increased respiratory rate and pulse rate were examined. We compared the characteristics among the young age group, middle age group, and advanced age group. RESULTS: The total number of patients was 204. In the young age group, the percentages of patients with irregular visits and non visits to a medical institution were high. This group showed high percentages of smokers and pet owners. The percentage of continuous ICS users in this group was 25.9%. The middle age group had high rates of aspirin-intolerant asthma. The percentage of continuous ICS users in this group was 60.2%. In the advanced age group, the percentages of patients with hypertension/heart disease, diabetes mellitus, and COPD were high. This group showed good treatment adherence. The percentage of continuous ICS users in this group was 77.4%. CONCLUSIONS: The characteristics of inpatients with severe asthma vary depending on age. We need to establish countermeasures for asthma exacerbation according to the characteristics of patients depending on age.

Increased interleukin-27 production by antigen-presenting cells promotes regulatory T cell differentiation and contributes to inducing a remission in patients with eosinophilic granulomatosis with polyangiitis.

BACKGROUND: We investigated the cytokine production profiles of antigen-presenting cells (APCs) and the status of patients with eosinophilic granulomatosis with polyangiitis (EGPA) in order to identify the cytokine profile that contributes to inducing differentiation of CD4(+) effector Th cells and regulatory T cells. METHODS: We counted the number of CD4(+)FOXP3(+) T cells, CD4(+)CD25(+)CTLA-4(+) T cells, CD4(+) T cells that predominantly produce IL-10 (Tr1 cells) and IL-17 (Th17 cells) and monocytes and monocyte-derived dendritic cells (mDCs) expressing Toll-like receptor (TLR)2 and TLR4 in the peripheral blood of 47 EGPA patients and 40 bronchial asthma patients (who did not have EGPA) and calculated the percentages of monocytes and mDCs that produced IL-23p19 and IL-27 in response to lipopolysaccharide (LPS) stimulation. RESULTS: Lower TLR4 expression was observed on the monocytes of relapsed EGPA patients and lower expression of both TLR2 and TLR4 on their mDCs than on the cells from EGPA patients in remission or non-EGPA patients. The percentages of monocytes expressing TLR4 were positively correlated with the percentages of regulatory T cells in peripheral blood. In addition, the percentages of monocytes and the percentages of mDCs that produced IL-27 and IL-23p19 in response to LPS stimulation were positively correlated with the percentages of Tr1 cells and Th17 cells in peripheral blood. A positive correlation was also found between the percentages of mDCs that produced IL-27 and the percentages of Tr1 cells. CONCLUSION: Increased dominancy of IL-23p19 and IL-27 production by the APCs of EGPA patients may be linked to differentiation of Th17 cells and Tr1 cells.

Decreases in the numbers of peripheral blood regulatory T cells, and increases in the levels of memory and activated B cells, in patients with active eosinophilic granulomatosis and polyangiitis.

PURPOSE: Eosinophilic granulomatosis with polyangiitis (EGPA), a rare disease characterized by the presence of allergic granulomatosis and necrotizing vasculitis, is often effectively treated with corticosteroids. However, relapse rates are high and, for unknown reasons, some EGPA patients suffer frequent relapses after entry into initial remission. Regulatory T (Treg) cells and B cells are implicated in the development and progression of EGPA. Here, we explored the influence of Treg cells and a co-stimulatory factor present on B cells on the development and course of EGPA. METHODS: We studied 45 EGPA patients (19 of whom experienced frequent relapses and 26 of whom seldom relapsed) and 67 (control) patients with general asthma. We determined the counts or percentages of whole-blood cells exhibiting the following characteristics: FOXP3(+) cells among CD4(+) Treg cells; CTLA-4(+) cells among CD4(+)/CD25(+) Treg cells; and CD27(+), CD80(+), CD86(+), or CD95(+) cells among CD19(+) B cells. We also measured serum IgG concentrations. RESULTS: Compared with patients with asthma or seldom-relapsing EGPA, frequently relapsing EGPA patients with active disease exhibited decreased counts of Treg cells and increased percentages of B cells that scored as CD80(+), CD27(+), or CD95(+). Patients with frequently relapsing EGPA had increased percentages of CD27(+) and CD95(+) B cells, and fewer CD19(+) B cells, than did patients in the other two groups. Lower CD19(+) B cell counts were associated with reduced Treg cell counts and a lower serum IgG concentration. CONCLUSION: In patients with frequently relapsing EGPA, decreases in Treg cell numbers and increased percentages of activated B cells may induce apoptosis of B cells.

Aspirin-intolerant asthma (AIA) assessment using the urinary biomarkers, leukotriene E4 (LTE4) and prostaglandin D2 (PGD2) metabolites.

The clinical syndrome of aspirin-intolerant asthma (AIA) is characterized by aspirin/nonsteroidal anti-inflammatory drug intolerance, bronchial asthma, and chronic rhinosinusitis with nasal polyposis. AIA reactions are evidently triggered by pharmacological effect of cyclooxygenase-1 inhibitors. Urine sampling is a non-invasive research tool for time-course measurements in clinical investigations. The urinary stable metabolite concentration of arachidonic acid products provides a time-integrated estimate of the production of the parent compounds in vivo. AIA patients exhibits significantly higher urinary concentrations of leukotriene E(4) (LTE(4)) and 1,15-dioxo-9α-hydroxy-2,3,4,5-tetranorprostan-1,20-dioic acid (tetranor-PGDM), a newly identified metabolite of PGD(2), at baseline. This finding suggests the possibility that increased mast cell activation is involved in the pathophysiology of AIA even in a clinically stable condition. In addition, lower urinary concentrations of primary prostaglandin E(2) and 15-epimer of lipoxin A(4) at baseline in the AIA patients suggest that the impaired anti-inflammatory elements may also contribute to the severe clinical outcome of AIA. During the AIA reaction, the urinary concentrations of LTE(4) and PGD(2) metabolites, including tetranor-PGDM significantly and correlatively increase. It is considered that mast cell activation probably is a pathophysiologic hallmark of AIA. However, despite the fact that cyclooxygenease-1 is the dominant in vivo PGD(2) biosynthetic pathway, the precise mechanism underlying the PGD(2) overproduction resulting from the pharmacological effect of cyclooxygenease-1 inhibitors in AIA remains unknown. A comprehensive analysis of the urinary concentration of inflammatory mediators may afford a new research target in elucidating the pathophysiology of AIA.

High-dose intravenous immunoglobulin treatment increases regulatory T cells in patients with eosinophilic granulomatosis with polyangiitis.

OBJECTIVE: We studied the effects of intravenous immunoglobulin (IVIG) treatment on clinical symptoms and regulatory T (Treg) cell frequency in patients with eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: Twenty-two EGPA patients with severe mononeuritis multiplex or cardiac dysfunction received IVIG therapy combined with conventional therapy (corticosteroid, immunosuppressants, or both). As a control, 24 EGPA patients without severe vasculitic symptoms were treated with conventional therapy. Before, during, and after treatment, we determined percentages of Treg cells and other relevant cells in patients' peripheral blood. RESULTS: The frequency of CD25+ among CD4+ T cells was lower at onset in the study group than in controls but increased significantly after IVIG treatment, relative to controls. The frequency of CD25+ among CD4+ T cells correlated with the frequency of FOXP3+ among CD4+ T cells and interleukin 10 produced by CD25+CD4+ T cells. CONCLUSION: The increase in Treg cells seen with the combination of IVIG and conventional therapy may promote remission in EGPA.

Persistent airflow obstruction in young adult asthma patients.

BACKGROUND: Lung function determined by spirometry and the severity of dyspnea correlate weakly in asthma patients. We attempted to determine the risk factors in asthma patients having persistent airway obstruction despite of having only mild subjective symptoms, and to examine the possibility of improving FEV1 by treating asthma on the basis of the bronchodilator change in FEV1. METHODS: We examined asthma patients in their 20s and who visited Sagamihara National Hospital for the first time over a period of four years, by reviewing their clinical records. They underwent tests on the bronchodilator change in FEV1 and a test of airway hyperresponsiveness to histamine dihydrochloride. RESULTS: One hundred thirty-eight subjects (mean age, 25.6 years; 51 males, 87 females; current smoking, 30.4%; history of childhood asthma, 48.6%) were enrolled. Among them, 18.8% (26/138) showed persistent airway obstruction (postbronchodilator FEV1/FVC (%) <80%). Using the multiple logistic regression model, we found that history of childhood asthma and smoking history were the significant isolated risk factors for persistent airway obstruction. Moreover, we determined that the factors associated with the reversibility of airway obstruction in asthma patients without subjective symptoms were history of childhood asthma. CONCLUSIONS: In this study, patients not undergoing treatment for asthma were examined. History of childhood asthma and smoking history may be the risk factors for persistent airway obstruction in the asthma patients with mild subjective symptoms. Tests on the bronchodilator change in FEV1 should be performed in patients with history of childhood asthma and smoking history, even if they have only mild subjective symptoms.

Allergenicity and cross-reactivity of booklice (Liposcelis bostrichophila): a common household insect pest in Japan.

BACKGROUND: Booklice (Liposcelis bostrichophila) are a common household insect pest distributed worldwide. Particularly in Japan, they infest 'tatami' mats and are the most frequently detected insect among all detectable insects, present at a frequency of about 90% in dust samples. Although it has been hypothesized that they are an important indoor allergen, studies on their allergenicity have been limited. METHODS: To clarify the allergenicity of booklice and the cross-reactivity of this insect allergen with allergens of other insects, patients sensitized to booklice were identified from 185 Japanese adults with allergic asthma using skin tests and IgE-ELISA. IgE-inhibition analysis, immunoblotting and immunoblotting-inhibition analysis were performed using sera from these patients. Allergenic proteins contributing to specific sensitization to booklice were identified by two-dimensional electrophoresis and two-dimensional immunoblotting. RESULTS: The booklouse-specific IgE antibody was detected in sera from 41 patients (22% of studied patients). IgE inhibition analysis revealed that IgE reactivity to the booklouse allergen in the sera from one third of booklouse-sensitized patients was not inhibited by preincubation with extracts from any other environmental insects in this study. Immunoblotting identified a 26-kD protein from booklouse extract as the allergenic protein contributing to specific sensitization to booklice. The amino acid sequence of peptide fragments of this protein showed no homology to those of previously described allergenic proteins, indicating that this protein is a new allergen. CONCLUSIONS: Sensitization to booklice was relatively common and specific sensitization to this insect not related to insect panallergy was indicated in this population.

[Allergic bronchopulmonary mycosis due to Schizophyllum commune and Aspergillus fumigatus].

A 53-year-old man who had been suffering from asthma presented to our hospital because of abnormal shadows detected on a chest X-ray film during a routine medical examination. A biopsy specimen of a mucus plug obtained by bronchoscopy showed fungal hyphae, eosinophils, and Charcot-Leyden crystals, with evidence of lung tissue eosinophilia. Schizophyllum commune and Aspergillus fumigatus were isolated from his sputum, bronchial washing specimens and the mucus plug. We detected specific immunoglobulin E anti-Aspergillus fumigatus responses and precipitating antibodies against Schizophyllum commune and Aspergillus fumigatus, which led to the diagnosis of allergic bronchopulmonary mycosis caused by both fungi. We gave him fluticasone/salmeterol and itraconazole; thereafter, his symptoms of cough and sputum production and his radiological findings all improved.