Sinobronchial Syndrome Research Articles

Prevalence and causes of chronic cough in Japan

BackgroundChronic cough is one of the most common symptoms of respiratory diseases and can adversely affect patients’ quality of life and interfere with social activities, resulting in a significant social burden. A survey is required to elucidate the frequency and treatment effect of chronic cough. However, clinical studies that cover all of Japan have not yet been conducted. MethodsPatients who presented with a cough that lasted longer than 8 weeks and visited the respiratory clinics or hospitals affiliated with the Japan Cough Society during the 2-year study period were registered. ResultsA total of 379 patients were enrolled, and those who did not meet the definition of chronic cough were excluded. A total of 334 patients were analyzed: 201 patients had a single cause, and 113 patients had two or more causes. The main causative diseases were cough variant asthma in 92 patients, sinobronchial syndrome (SBS) in 36 patients, atopic cough in 31 patients, and gastroesophageal reflux (GER)-associated cough in 10 patients. The time required to treat undiagnosed patients and those with SBS was significantly longer and the treatment success rate for GER-associated cough was considerably poor. ConclusionsWe confirmed that the main causes of chronic cough were cough variant asthma, SBS, atopic cough, and their complications. We also showed that complicated GER-associated cough was more likely to become refractory. This is the first nationwide study in Japan of the causes and treatment effects of chronic cough.

A Study on Cough Sensitivity and Airway Inflammation in Patients with Sinobronchial Syndrome.

Objective This study aimed to clarify the characteristics of cough-reflex sensitivity and airway inflammation in patients with sinobronchial syndrome (SBS). Methods 39 patients with SBS, 53 patients with upper airway cough syndrome (UACS) induced by rhinitis, 33 patients with chronic sinusitis without cough, and 39 healthy controls (HCs) were enrolled between January 2013 and December 2018. All participants underwent a capsaicin cough-sensitivity test and cytology of induced sputum. The concentration of calcitonin-gene-related peptide (CGPR), histamine, prostaglandin (PG) E2, and eosinophil cationic protein (ECP) in induced sputum were measured using enzyme-linked immunosorbent assays (ELISAs). Results The lowest concentration of capsaicin solution that induced ≥5 coughs (C5) was decreased markedly in patients with UACS induced by rhinitis compared with SBS patients (1.95 ± 2.92 vs. 31.2 ± 58.6 mol/L, P < 0.001), indicating higher cough-reflex sensitivity among UACS patients induced by rhinitis. However, there was no difference of these threshold between SBS patients and patients with sinusitis without cough and HCs. The percentage of neutrophils in sputum was increased remarkably in patients with SBS compared with HCs (40.0 ± 48.5% vs. 5.5 ± 9.0%, P < 0.001). A higher concentration of CGPR, histamine, and PGE2 was observed in induced sputum from patients with UACS induced by rhinitis than that in controls, and the ECP level was increased significantly in UACS induced by rhinitis compared with that in the other three groups. Conclusions Cough-reflex sensitivity and airway inflammation in patients with SBS were different in patients with UACS induced by rhinitis. Thus, the mechanism of cough in those two patient populations might differ. Our study is registered in the Chinese Clinical Trials Register (https://www.chictr.org.cn/) as ChiCTR-TRC-00000152.

Sinobronchial Syndrome Patients with Suspected Non-Tuberculous Mycobacterium Infection Exacerbated by Exophiala dermatitidis Infection

BackgroundExophiala dermatitidis is an environmental black fungus that rarely causes respiratory infections, yet its pathophysiological features and treatment regimens have not been established.Case SeriesTwo cases of exacerbations of chronic bronchitis and sinusitis due to E. dermatitidis infection in Japan are presented. Both patients were women, and non-tuberculous Mycobacterium (NTM) infection was suspected based on chest radiological findings, but E. dermatitidis was detected from bronchial lavage fluid and nasal mucus, respectively. Both cases were successfully treated by antifungal agents such as liposomal amphotericin B, voriconazole, and itraconazole, but clarithromycin, rifampicin, ethambutol, and sitafloxacin for NTM were not effective.ConclusionE. dermatitidis can become a respiratory pathogen, especially in patients with chronic sinobronchial syndrome.

The Japanese respiratory society guidelines for the management of cough and sputum (digest edition)

Cough and sputum are common complaints at outpatient visits. In this digest version, we provide a general overview of these two symptoms and discuss the management of acute (up to three weeks) and prolonged/chronic cough (longer than three weeks). Flowcharts are provided, along with a step-by-step explanation of their diagnosis and management. Most cases of acute cough are due to an infection. In chronic respiratory illness, a cough could be a symptom of a respiratory infection such as pulmonary tuberculosis, malignancy such as a pulmonary tumor, asthma, chronic obstructive pulmonary disease, chronic bronchitis, bronchiectasis, drug-induced lung injury, heart failure, nasal sinus disease, sinobronchial syndrome, eosinophilic sinusitis, cough variant asthma (CVA), atopic cough, chronic laryngeal allergy, gastroesophageal reflux (GER), and post-infectious cough. Antibiotics should not be prescribed for over-peak cough but can be considered for atypical infections. The exploration of a single/major cause is recommended for persistent/chronic cough. When sputum is present, a sputum smear/culture (general bacteria, mycobacteria), cytology, cell differentiation, chest computed tomography (CT), and sinus X-ray or CT should be performed. There are two types of rhinosinusitis. Conventional sinusitis and eosinophilic rhinosinusitis present primarily with neutrophilic inflammation and eosinophilic inflammation, respectively. The most common causes of dry cough include CVA, atopic cough/laryngeal allergy (chronic), GER, and post-infectious cough. In the last chapter, future challenges and perspectives are discussed. We hope that the clarification of the pathology of cough hypersensitivity syndrome will lead to further development of "pathology-specific non-specific therapeutic drugs" and provide benefits to patients with chronic refractory cough.

Sinobronchial allergic mycosis syndrome in an elderly male

BackgroundAllergic bronchopulmonary aspergillosis (ABPA) and allergic fungal rhinosinusitis (AFRS) are characterized by hyper-responsiveness of the respiratory tract and the nasal cavity and paranasal sinuses, respectively to Aspergillus species and AFRS causes chronic rhinosinusitis. Herein, we report the first case of sinobronchial allergic mycosis (SAM) syndrome, defined as ABPA with concomitant AFRS, caused by Aspergillus fumigatus patient > 80 years.Case presentationAn 82-year-old male with interstitial pneumonia who returned for follow-up exhibited high-attenuation mucus plug in the right intermediate bronchial trunk, infiltration in the right lung field, and right pleural effusion on regular chest computed tomography (CT). We found unilateral central bronchiectasis in the right upper lobe. Similarly, CT scan of the paranasal sinuses revealed high-attenuation mucus plugs in left ethmoid sinuses. Biopsy specimens from the plugs in the right intermediate bronchial trunk and the left ethmoid sinuses revealed allergic mucin with layers of mucus eosinophils, eosinophil-predominant mixed inflammatory cell infiltrate and Aspergillus hyphae. The patient fulfilled all the major criteria for ABPA and AFRS, and was diagnosed with SAM syndrome. CT scan of the lung and paranasal sinuses revealed apparent amelioration after oral steroid therapy.ConclusionDespite mostly reported in relatively young patients, SAM syndrome can occur in elderly individuals as well.

A Cross-sectional Survey of the Clinical Manifestations and Underlying Illness of Cough.

The aim of this study was to identify factors affecting the final diagnosis of cough. This study recruited 463 consecutive patients who visited five Japanese general hospitals due to cough from October 2006 to September 2007. Of these, 418 patients (90%) who completed a questionnaire designed to acquire data regarding clinical manifestations of cough were included. Most patients with bronchial asthma had cough with seasonal variation and wheezing. Patients with gastro esophageal reflux disease suffered from heartburn and cough without daily or seasonal variation. Cough associated with sinobronchial syndrome was only observed in females and was linked to increased sputum. Patients with whooping cough were bothered by cough interrupting sleep and talking. Patients with cardiogenic cough had exertional dyspnea. The specific items on our questionnaire relating to patient characteristics, complications, and triggers of cough, represent useful tools for diagnosing the primary disease producing cough.

Effectiveness of clarithromycin in patients with yellow nail syndrome

BackgroundYellow nail syndrome (YNS) is a rare disease characterized by the triad of thickened, slow-growing yellow nails, lymphedema, and chronic respiratory manifestations. The cause of YNS is not known; however, it is suggested to be due to a congenital lymph abnormality. Since YNS is accompanied by chronic bronchial infection in more than half of patients, we hypothesized that treatment with clarithromycin (CAM) could be effective. We therefore evaluated the effectiveness of CAM against nail discoloration and respiratory manifestation in patients with YNS.MethodsWe conducted an observational study involving 5 patients with YNS who were treated at our institution between January 2005 and January 2016. CAM was prescribed for every patient. Patient demographic information, comorbidities, medications, chest radiographs, and clinical data such as nail color were extracted to evaluate clinical outcome.ResultsMean patient age was 71.6 years, and 2 patients (40%) were male. Four patients had sinusitis, and 2 had rheumatoid arthritis. Regarding respiratory manifestations, 4 patients had sinobronchial syndrome and 2 had pleural effusion. Nail discoloration improved in every patient after CAM treatment. Four patients also experienced improvement in their respiratory manifestations.ConclusionsIn patients with YNS, the anti-inflammatory activity of macrolides might improve their systemic inflammation. This improvement could help to reduce lymphedema and promote nail growth.Trial registrationEthical approval was provided by the institutional review board of the National Center of Global Health and Medicine (NCGM-G-002143-00), in January 2017. This study is retrospectively registered for UMIN Clinical Trial Registry (UMIN000028514) in August 4th, 2017.

Effect of Ipratropium Bromide on Airway Cough Sensitivity to Inhaled Capsaicin in Patients with Asthma and Sinobronchial Syndrome

Effect of Ipratropium Bromide on Airway Cough Sensitivity to Inhaled Capsaicin in Patients with Asthma and Sinobronchial Syndrome

Sinobronchial syndrome と気道過敏性との関連(気道過敏性と気管支学的諸問題)

Sinobronchial syndrome と気道過敏性との関連(気道過敏性と気管支学的諸問題)

An analysis of etiology, causal pathogens, imaging patterns, and treatment of Japanese patients with bronchiectasis.

Bronchiectasis (BE), a syndrome that presents with persistent or recurrent bronchial sepsis related to irreversibly damaged and dilated bronchi, has not been well-characterized in Asians. This study aims to review the etiology, causal pathogens, imaging patterns, and treatment of BE and to define the prognostic factors for acute exacerbation in a Japanese population. We performed a retrospective cohort study of 147 patients (104 women; median age, 73 years; range, 30-95 years) with BE at our institution using high-resolution computed tomography to identify imaging patterns and the area of pulmonary involvement. Common BE etiologies were idiopathic (N=50 [34%]), sinobronchial syndrome (N=37 [25%]), non-tuberculous mycobacteriosis (NTM; N=26 [18%]), and previous respiratory infection (N=21[14%]). Pseudomonas aeruginosa was the most common causal pathogen (24%). Common imaging patterns were cylindrical (66%) and mixed including cylindrical pattern (47%). The median number of involved lobes was 2; 49% of the patients had ≥ 3 involved lobes, and 49% had middle lobe and left lingula dominant BE. Patients with predominantly lower lobe BE comprised 4% of the NTM group and 48% of the non-NTM group (P<0.001). In multivariate analysis, cystic BE was a predictor for frequent exacerbations in non-NTM patients (OR=7.947; P=0.004) which led to increased hospital admissions (OR=4.691; P=0.004). Idiopathic and sinobronchial syndrome were common causes of BE. Etiology did not contribute to imaging pattern or predictors of exacerbations. Cystic BE was a predictor for frequent exacerbations in the non-NTM BE patients.

Classification of chronic cough by systematic treatment cascade trial starting with beta agonist

BackgroundChronic cough is one of the most challenging symptoms to diagnose and treat, not only because of the variety of underlying disorders but also its varying susceptibility to treatments. Etiological studies of chronic cough vary depending on the clinical settings and the particular interests of investigators.ObjectivesThe purposes of this study were first to categorize the etiology of chronic cough by its response to systematic diagnostic treatments starting from the β2 agonist and second to sub-categorize β2 agonist responsive cough (BRC) by the airway hyperresponsiveness.MethodsOne hundred and eighty-four never-smokers received the maximal dose of procaterol to diagnose BRC. BRC was sub-categorized into two groups with or without airway hyperresponsiveness measured by the methacholine challenge test. Sinobronchial syndrome (SBS) was diagnosed by postnasal drip symptoms and by the response to clarythromycin and carbocysteine. Atopic cough (AC) was diagnosed by the evidence of atopy and the response to cetirizine hydrochloride. Gastroesophageal reflux disease (GERD) was diagnosed by the response to rabeprazole sodium. Since we did not investigate eosinophil counts in the tissue or in the induced sputum, no diagnosis of eosinophilic bronchitis was made.ResultsOne hundred and nine patients had BRC. Twenty-three of them had bronchial asthma (BA), 53 had cough variant asthma (CVA) and 33 had non-hyperresponsive BRC (NHBRC). Thirty-one patients had GERD, 27 had AC and 14 had SBS. Twenty-five patients had more than one diagnosis in combination, while 6 had other miscellaneous diseases. Twelve patients were undiagnosed and 11 dropped out of the study.ConclusionsThe majority of chronic cough was BRC. NHBRC was a new chronic cough entity. GERD is a common cause of chronic cough in Japan, as in Western countries. AC and SBS are also causes of chronic cough in Japan.Trial registrationUniversity hospital medical information network (UMIN 000007483)

慢性咳嗽診断における耳鼻咽喉科と呼吸器内科との連携&amp;mdash;副鼻腔気管支症候群を1例に&amp;mdash;

慢性咳嗽診断における耳鼻咽喉科と呼吸器内科との連携&amp;mdash;副鼻腔気管支症候群を1例に&amp;mdash;

Macrolide Therapy in Chronic Inflammatory Diseases

Sinobronchial syndrome is well accepted to involve the coexistence of chronic rhinosinusitis (CS) and chronic lower airway inflammation such as chronic bronchitis and diffuse panbronchiolitis (DPB). Although these diseases are resistant to several types of treatment, after discovery of the effectiveness of erythromycin on DPB, low-dose and long-term administration of macrolide antibiotics such as erythromycin, roxithromycin, and clarithromycin, are used frequently in the treatment of these diseases with remarkable success [1]. It has also reported that long-term use of azithromycin, a 16-membered macrolide antibiotic, can improve the lung functions in patients with cystic fibrosis (CF) [2]. These reports clearly indicate that the prognosis of these life-threatening airway diseases, especially DPB and CF, may improve dramatically, but the mode of action of this macrolide therapy is not fully understood. Furthermore, there is little information about the kind of diseases, which can be treated with the macrolide therapy.

A Case of Sinobronchial Syndrome Complicated with Myeloperoxidase Antineutrophil Cytoplasmic Antibody Associated Vasculitis: Review of the Literature

We report a case of long-standing sinobronchial syndrome complicated by microscopic polyangiitis (MPA) during the clinical course. The patient showed a mild elevation of myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) 17 months prior to the diagnosis of MPA. Subsequently, her MPO-ANCA level gradually became more elevated, and finally her MPO-ANCA level peaked when purpura appeared. Histologic examination of the skin biopsy was consistent with leukocytoclastic vasculitis. Based on the pathological and clinical findings, a diagnosis of MPA was made. Corticosteroid therapy finally led to a remission of MPA with normalized MPO-ANCA titers.

Two Cases With Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma Successfully Treated With Clarithromycin

A 70-year-old woman with a history of sinobronchial syndrome was admitted to the hospital because of a cough, sputum, and abnormal chest shadow. She was diagnosed with pulmonary mucosa-associated lymphoid tissue lymphoma (p-MALToma) based on results of a pathologic examination and the gene rearrangements in the Ig heavy chain on Southern blot hybridization. Although p-MALToma did not regress with conventional therapy, it was reduced after long-term treatment with clarithromycin (CAM) (200 mg/d). A 57-year-old woman with a history of Sjögren syndrome and lymphocytic interstitial pneumonia had a mass lesion in the left lower lung field. CT image-guided biopsy established a diagnosis of p-MALToma. The p-MALToma regressed with long-term treatment with CAM (200 mg/d), whereas Helicobacter pylori (HP) eradication therapy was not effective in concurrent atrophic gastritis with HP. It is suggested that CAM, a macrolide antibiotic, may be effective in some patients with p-MALToma.

Induced Sputum Concentrations of Mucin in Patients With Asthma and Chronic Cough

Mucus hypersecretion is an important pathophysiologic index of airway disease. Measurement of secreted mucin in sputum has been reported in asthma, but not in chronic cough with or without increased sputum production. We studied 49 patients with classic asthma (CA), 39 with cough-variant asthma (CVA), nine and five with chronic cough associated with sinobronchial syndrome (SBS) and gastroesophageal reflux disease (GERD), respectively, and 11 healthy controls. Seventeen patients with CA, but none from the other groups, were taking antiinflammatory medications. Mucin levels in induced sputum supernatants were measured by enzyme-linked immunosorbent assay, which detects airway mucin, probably including MUC5AC and MUC5B. Mucin levels were higher in patients with CA (674.2 +/- 548.8 microg/mL) and SBS (638.4 +/- 650.7 microg/mL) than in controls (212.0 +/- 167.1 microg/mL) (P = .0037 and .044). They were also higher in patients with CA than in those with CVA (350.4 +/- 374.0 microg/mL) and GERD (134.3 +/- 93.1 microg/mL) (P = .0016 and 0.015), but results did not differ between the latter groups and controls. When the four disease groups were combined, patients with frequent sputum production had greater mucin levels than those with occasional (P = .0023) or no sputum production (P < .0001). Patients with CA showed negative correlations of mucin levels with respiratory resistance indices on impulse oscillation and with airway sensitivity to methacholine. Sputum mucin levels differ in various respiratory conditions when compared with controls, primarily reflecting the degree of sputum production. Airway mucin might possibly exert protective effects in asthma, at least between exacerbations, but this issue needs to be further clarified by future studies.

Deterioration of Asthma in a Patient With Diffuse Panbronchiolitis (DPB) After Macrolide Therapy

Diffuse panbronchiolitis (DPB), an important cause of progressive obstructive lung disease in the Far East, is a distinctive sinobronchial syndrome with characteristic radiologic and histologic features. Asthma is a chronic inflammatory disease characterized by airway narrowing. The major inflammatory cells involved in the pathogenesis of asthma are type 2 helper T (Th2) cells, eosinophils, and mast cells. The authors’ patient was diagnosed with DPB and asthma. Although macrolide therapy led to the disappearance of the radiologic abnormalities indicating centrilobular nodular lesions, the respiratory symptoms and pulmonary function worsened. Administration of inhaled corticosteroids improved the respiratory symptoms and pulmonary function. To the authors’ knowledge, no case of DPB with asthma has been reported in the English-language literature.

Sputum leukotrienes in chronic airway diseases and bronchial asthma attacks

To determine the pathogenetic role of leukotrienes in chronic airway diseases, sputum samples from patients with bronchial asthma (BA), diffuse panbronchiolitis (DPB), sinobronchial syndrome (SBS), and bronchiectasis (BE) were examined for the presence of leukotrienes (LT) C4, D4, E4, B4, all apparently derived from airway inflammatory cells. Sputum samples from 21 patients, including 10 with BA attack (5 atopic type, 5 non-atopic type) and 11 with chronic obstructive airway diseases (3 DPB, 6 SBS, and BE), were studied. Patients expectorated sputum directly into test-tubes containing 80% ethanol. Following ethanol extraction and partial purification by a C18 SEP-PAK column, LTs were further purified by high performance liquid chromatography (HPLC). Fractions from HPLC with elution times corresponding to synthetic LTC4, D4, E4, and B4 were used to quantify LTs by radioimmunoassay. Eosinophils and neutrophils in the sputum (0.5 ml) were counted following Papanicolaou staining. Percentages of eosinophils in sputum were higher in BA, while those of neutrophils were higher in DPB. Sputum levels of LTC4 were 1.2 +/- 1.6 in BA, 0.12 +/- 0.11 in SBS, and 0.42 +/- 0.14 ng/ml in DPB. Those of LTD4 were 0.21 +/- 0.27 in BA, 0.9 +/- 0.13 in DPB, and 0.10 +/- 0.07 in SBS. LTE4 levels were 5.06 +/- 3.83 in DPB and 2.66 +/- 4.32 in BA. Levels of LTB4 were 1.36 +/- 1.19 in DPB, 0.28 +/- 0.27 in BA, 0.12 +/- 0.07 in SBS, and 0.04 +/- 0.04 in BE. In asthmatics, peptide leukotriene content in sputum was higher than that in chronic airway disease patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of erythromycin on mucociliary transport and clinical symptoms in patients with sinobronchial syndrome

The effect of erythromycin (EM) on mucociliary transport function assessed by saccharin test and clinical symptoms were studied in 19 patients with sinobronchial syndrome (SBS). Before treatment with EM, the mean nasal clearance time (NCT) of SBS patients was 51.9 +/- 40.5 (SD) min, which was significantly (p < 0.01) longer than that of control subjects (12.4 +/- 5.3 min). After 4-week treatment with oral EM (600 mg/day), NCT of SBS patients significantly (p < 0.01) improved (29.2 +/- 34.2 min). In 11 of 19 SBS patients, bacteria from sputum culture disappeared after EM therapy. Frequency of cough and volume of sputum were significantly (p < 0.05) decreased by EM therapy. Nasal symptoms (such as nasal obstruction and rhinorrhea) were also significantly (p < 0.05) improved by EM therapy. These findings suggested that disorder of mucociliary transport function was present in patients with SBS, and EM therapy improved this function. EM clinically improved not only the lower airway symptoms, but also the nasal symptoms.

Two Probable Cases of Adult Williams-Campbell Syndrome

Williams-Campbell syndrome is a unique type of bronchiectasis which shows ballooning during expiration and collapse during inspiration. Its etiology is thought to be a congenital decrease in bronchial cartilage. We experienced two adult cases of Williams-Campbell syndrome. Since the mucociliary transport system was normal in both cases and neither case had chronic sinusitis, these cases differed from sino-bronchial syndrome. Cases of Williams-Campbell syndrome reported in Japan show characteristic bronchography, but a decrease in bronchial cartilage may or may not be present and its congenital nature is very difficult to demonstrate. We therefore advocate referring to such cases of bronchiectasis with these bronchographic characteristics Williams-Campbell-type bronchiectasis, even if a decrease in bronchial cartilage is not observed.