Haruhiko Ogawa

Eosinophilic tracheobronchitis and airway cough hypersensitivity in chronic non‐productive cough

We have shown that some patients presenting with chronic bronchodilator‐resistant non‐productive cough have global atopic tendency and airway cough hypersensitivity without non‐specific bronchial hyperresponsiveness, abbreviated as atopic cough. The cough is successfully treated with histamine H1‐antagonists and/or glucocorticoids.

Importance of atopic cough, cough variant asthma and sinobronchial syndrome as causes of chronic cough in the Hokuriku area of Japan

Objective:  A prospective multicentre study was conducted to elucidate the causes of chronic cough in Japan.

Efficacy of Itraconazole in the Treatment of Patients with Chronic Cough Whose Sputa Yield Basidiomycetous Fungi—Fungus-Associated Chronic Cough (FACC)

Objectives. This controlled study was performed to clarify the therapeutic benefit of itraconazole for the treatment of patients with chronic cough, wherein a sputum culture yielded basidiomycetous (BM) fungi. Methods. Of the 171 patients who visited our hospital for the diagnosis and treatment of chronic cough, BM was detected in the sputum of 39 patients. Informed consents were obtained from 21 patients who were subsequently enrolled in this trial. After the administration of the standard therapy, all the patients were enrolled in a randomized placebo-controlled study with 2 weeks of treatment with a low dose of itraconazole (50 mg/day) (n = 10) in comparison with a corresponding period of treatment with matched placebo (ambroxol hydrochloride 45 mg/day) (n = 11). Coughing was assessed using subjective cough symptom scale and capsaicin cough challenging. Results. The treatment with itraconazole, but not placebo (p = 0.17), was associated with a significant improvement in the cough scale (p = 0.0051); moreover, the improvement achieved with itraconazole was significant (p < 0.001) when compared with that of the placebo. Conclusions. Low-dose itraconazole was shown to be an effective antitussive in patients with chronic cough in which sputum examination yielded BM fungi. The 21 patients described here entailed the following manifestations: (1) chronic cough; (2) the presence of environmental fungi, particularly basidiomycetous (BM) fungi, in the sputum; and (3) good clinical response to antifungal drugs. These clinical features may constitute a unique disease concept called fungus-associated chronic cough (FACC).

The importance of basidiomycetous fungi cultured from the sputum of chronic idiopathic cough:: A study to determine the existence of recognizable clinical patterns to distinguish CIC from non-CIC

BACKGROUND Recently we have reported 5 cases of allergic fungal cough (AFC), which is intractable and is characterized by sensitization to one of basidiomycetous fungus. Because AFC shows good clinical response to antifungal drugs, diagnosing AFC in patients with CIC may lead to the consequent management of CIC. Therefore, we determined the incidence of CIC among our hospital patients, and the frequency of BM fungi in sputum samples collected from patients with CIC. Furthermore we evaluated whether or not a recognizable clinical pattern that distinguishes CIC from non-CIC exists. METHODS The medical records of 70 patients complaining of chronic cough who were referred to our hospital for diagnosis and treatment were analyzed retrospectively. RESULTS The primary diagnoses were CIC (27.0%), cough-variant asthma (30.0%), atopic cough (24.3%), sinobronchial syndrome (8.6%), cough-predominant asthma (7.1%), gastro-esophageal reflux (1.4%), and others (1.4%). In CIC patients, the median age, proportion of females, and frequency of acute upper respiratory tract infection did not differ significantly from those in non-CIC patients. CIC patients had a longer median duration of cough (11.0 months vs. 3.5 months). The positive ratio of BM cultured from the sputa of CIC patients (62.5%) was significantly (p=0.0061) higher than that of non-CIC patients (16.7%). CONCLUSION The existence of BM fungi in induced sputum may be an important factor for distinguishing the clinical manifestation of CIC from that of non-CIC. The clinical approach from the aspect of fungal allergy may serve as a clue that may aid in the successful management of CIC.

Seasonal chronic cough with sputum eosinophilia caused by Trichosporon cutaneum (Trichosporon asahii).

The case of a 46-year-old man with a chronic cough with sputum eosinophilia (atopic cough) caused by Trichosporon cutaneum serotype II (Trichosporon asahii) is reported. The diagnosis was made with the inhalation challenge test with T. asahii antigen. He was admitted for the diagnosis and treatment of a severe nonproductive cough in the summer season. Although his sputum contained 13% eosinophils of nucleated cells, he did not have bronchial hyperresponsiveness to methacholine or a heightened bronchomotor tone. Bronchodilator therapy was not effective for his cough. His symptoms worsened on returning home, suggesting the existence of some etiologic agent in his house. A high titer of serum anti-Trichosporon antibody was detected and antigen provocation test with the Trichosporon extract was positive: the development of a cough 6 h later and a decrease in the cough threshold to inhaled capsaicin 48 h later (7.85 μM from 31.3 μM prechallenge). This is the first report on a chronic cough with sputum eosinophilia induced by T. cutaneum (T. asahii).

Is Bjerkandera adusta Important to fungus-associated chronic cough as an allergen? Eight cases' reports.

Background. Recently, we have reported a new clinical disease concept called fungus-associated chronic cough (FACC), which entailed the following manifestations: (1) chronic cough; (2) the presence of environmental fungi, particularly basidiomycetous (BM) fungi, in the sputum; and (3) good clinical response to antifungal drugs. To clarify the relationship between the exposure to environmental fungi and the development of cough attacks, we reviewed the clinical records of patients with FACC and performed a molecular biological analysis of the BM fungi. Methods. We successfully selected 8 patients with chronic cough, wherein a sputum culture yielded B. adusta beforehand; moreover, we conducted allergological tests such as the immediate-type skin test, a serological test, bronchoprovocation test, and lymphocyte stimulation test (LST), using the antigenic solution of B. adusta. The efficacy of individualized therapy and the clinical manifestations in the eight patients were examined. Results. All the eight patients were diagnosed with FACC. Although three patients who did not show a positive reaction to the bronchoprovocation test or LST showed excellent clinical response to anti-fungal drugs; other 5 patients who showed a positive reaction to the bronchoprovocation test and/or LST seemed to be more intractable because of taking a longer time for complete remission and more frequent recurrence of cough. Conclusion. It was suggested that so-called allergic fungal cough (AFC), which is characterized by sensitization to B. adusta, may be included in a part of chronic intractable cough.

The Definitive Diagnostic Process and Successful Treatment for ABPM Caused by Schizophyllum commune: A Report of Two Cases

BACKGROUND Although mucoid impaction of the bronchi (MIB) is a well-known manifestation in allergic bronchopulmonary mycosis (ABPM), when unknown samples or plural eumycetes are cultured from bronchial materials, several problems are encountered which can affect the definitive diagnostic process or successful treatment. CASE SUMMARY The definitive diagnostic process of two patients [a 58-(Case 1) and a 70-(Case 2) year-old female] with MIB was: 1) to identify the existence of any allergic respiratory disorder, 2) to detect the fungi obtained from bronchial materials, with use of the 28S rDNA sequencing and analysis, 3) to investigate whether the detected fungus was a probable etiologic antigen, and 4) to make the final diagnosis based on the results of the inhalation examinations using the antigenic solution of the fungi. As a treatment strategy, bronchial toilet and low dose itraconazole therapy were planned according to the clinical manifestations of each patient. DISCUSSION The two patients with MIB were successfully diagnosed as ABPM caused by Schizophyllum commune (Sc-ABPM) accompanied with hyperattenuating mucoid impaction. The reliability of some allergological makers as a substitution for the bronchoprovocation test should be clarified in near future. Clinical manifestations demonstrated in our cases suggested that the allergic reaction such as eosinophilic bronchoalveolitis spreading around the mucus plug was a primary lesion underlying the Sc-ABPM. The success of the treatment for Sc-ABPM will be achieved by the strategy targeting to fundamental condition and by the control of the disease recurrence by means of effective environmental management.

Treatment of Atopic Cough Caused by Basidiomycetes Antigen with Low-dose Itraconazol

We report two patients with atopic cough due to Basidiomycetes antigen. One patient was a 27 year-old woman and the other was a 17 year-old boy. Both patients visited our hospital because of severe nonproductive cough. They did not have bronchial hyperresponsiveness to methacholine or heightened bronchomotor tone. Bronchodilator therapy was not effective for their cough. Her symptoms worsened in her office and his in his house, suggesting existence of etiologic agent(s) in their environments. Basidiomycetes was isolated from the woman’s office and from the boy’s house, and the bronchoprovocation test with Basidiomycetes antigen was positive. Low dose itraconazol (50 or 100 mg/day) given for two weeks eliminated cough in both patients. This is the first report describing the effectiveness of low dose antifungal therapy for atopic cough caused by Basidiomycetes antigen

Allergic Bronchopulmonary Fungal Disease Caused by Saccharomyces cerevisiae

We describe a patient who presented with dry cough, low‐grade fever, and focal patchy shadow of pulmonary infiltrates. Remarkably, the prospective etiological agent, Saccharomyces cerevisiae was purely and repeatedly cultured from her sputum. Allergic bronchopulmonary mycosis (ABPM) was diagnosed based on clinical, serological, and pathological criteria. Although the patient described here satisfied only three of the criteria, the conclusion that the allergic bronchopulmonary disease in our case was induced by S. cerevisiae was made based on the following evidence: 1) S. cerevisiae was repeatedly isolated from the patients sputum, 2) anti‐S. cerevisiae antibody was detected in her serum, and 3) bronchoprovocation test to S. cerevisiae antigen was positive. We present here a case of allergic bronchopulmonary fungal disease caused by S. cerevisiae antigen.

Eosinophilic bronchitis presenting with only severe dry cough due to bucillamine

Introduction Although an increasing number of drugs have been implicated in the aetiology of eosinophilic pneumonia characterized by the development of pulmonary infiltrates and peripheral blood eosinophilia, eosinophilic bronchitis without alveolitis due to some pharmacologic agents has not been reported. Bucillamine [N-(2-mercapto-2-methylpropionyl)-Lcystenine] is a commonly used drug for treatment of rheumatoid arthritis in Japan, which has recently been added to the growing list of pharmacologic agents associated with infiltrative pulmonary lesions. A case of eosinophilic bronchitis induced by this drug presenting with only severe dry cough is described. The results of transbronchoscopic bronchial biopsy, a lymphocyte stimulation test, and a challenge test supported this diagnosis.