Analysis of anticholinergic drugs associated with aspiration pneumonia using the Japanese adverse drug event report database: Supplementary insights from a scoping review.

BACKGROUND: Japan's super-aged society presents significant challenges, particularly with regard to managing aspiration pneumonia among older adults. We aimed to investigate the link between anticholinergic drug use and the incidence of aspiration pneumonia, primarily utilizing data from the Japanese Adverse Drug Event Report (JADER) database. METHODS: The primarily analysis included JADER data from the first quarter of 2004 through the third quarter of 2023, focusing on 2367 cases of aspiration pneumonia in individuals aged ≥60 years. The study examined the association of aspiration pneumonia with 49 drugs listed in the Anticholinergic Risk Scale, using the Reporting Odds Ratio for signal detection. A scoping review incorporating findings from MEDLINE and the Cochrane Library was conducted to validate these associations. RESULTS: The primary analysis identified an increased risk of aspiration pneumonia associated with specific drugs, including clozapine, haloperidol, risperidone, quetiapine, and olanzapine. A total of 20 drugs were significantly associated with an increased risk of aspiration pneumonia. Our results emphasize the importance of considering the dopamine-blocking effects of these drugs, particularly in at-risk populations, such as older adults, and those with conditions, such as schizophrenia or Parkinson's disease. CONCLUSIONS: The study highlights the importance of careful monitoring of anticholinergic drugs with potent dopamine-blocking effects, such as clozapine, haloperidol, risperidone, quetiapine, and olanzapine, to reduce the risk of aspiration pneumonia. Future research should include observational and interventional studies to further investigate these findings. ETHICS AND DISSEMINATION: As this study utilized pre-existing anonymized information, approval from an ethics committee was not required.

Prevalence and causes of chronic cough in Japan.

BACKGROUND: Chronic 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. METHODS: Patients 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. RESULTS: A 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. CONCLUSIONS: We 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.

Criteria for diagnosing aspiration pneumonia in Japan - A scoping review.

Aspiration pneumonia accounts for a significantly higher proportion of pneumonia cases in Japan than in Western countries. We conducted a scoping review of the criteria for diagnosing aspiration pneumonia in the literature on aspiration pneumonia reported from Japan, where the incidence of aspiration pneumonia is higher than in Europe and the United States. We searched MEDLINE and the Cochrane Library as literature databases. The search keywords were "aspiration," "pneumonia," and "Japan," combined with AND. After eliminating duplicates, we screened 852 articles and reviewed 112 articles in full, with 58 articles included in the final analysis. Of the 58 articles, 25 adopted the clinical diagnostic criteria for aspiration pneumonia proposed by the Japanese Study Group on Aspiration Pulmonary Disease. The remaining 33 articles used their own diagnostic criteria. There were 12 articles that described the features of images. There were three articles stating that aspiration pneumonitis should be excluded. There were five reports in which all patients were examined for swallowing function disorder. In Japan, the diagnostic criteria for aspiration pneumonia proposed by the Japanese Study Group on Aspiration Pulmonary Disease were used extensively, and various other criteria were also used. Aspiration pneumonia diagnosed according to different criteria should be carefully compared in terms of incidence, therapeutic effects, and prognosis.

Effect of aspiration on the lungs in children: a comparison using chest computed tomography findings.

BACKGROUND: Detecting and addressing aspiration early in children with dysphagia, such as those with cerebral palsy, is important for preventing aspiration pneumonia. The current gold standards for assessing aspiration are swallowing function tests, such as fiberoptic endoscopic evaluation of swallowing (FEES) and videofluorographic swallowing study; however, the relationship between aspiration of secretion vs aspiration of foodstuff and pulmonary injury is unclear. To clarify this relationship, we examined the correlations between pneumonia findings from chest computed tomography (CT) and the presence or absence of aspiration detected by FEES. METHODS: Eighty-five children (11 years 2 months ±7 years 2 months) underwent FEES and chest CT. Based on the FEES findings, the participants were divided into groups: with and without food aspiration, and with and without saliva aspiration. Correlations between chest CT findings of pneumonia and the presence or absence of each type of aspiration were then examined. RESULTS: No significant correlations were observed between food aspiration and chest CT findings of pneumonia, whereas saliva aspiration and chest CT findings of pneumonia were significantly correlated. In addition, saliva aspiration was significantly associated with bronchial wall thickening (p < 0.01) and atelectasis (p < 0.05). CONCLUSIONS: Our findings in children suggest that: (1) the presence or absence of food aspiration detected by FEES evaluation has little correlation with pneumonia, and (2) the presence or absence of saliva aspiration may be an indicator of aspiration pneumonia risk.

Effect of pressure stress applied to the airway on cough-reflex sensitivity in Guinea pigs.

RATIONALE: We hypothesized that cough stress of the airway wall results in a self-perpetuating cough-reflex cycle in which antigen-induced increase in cough-reflex sensitivity results in pathologic cough, and the cough in turn further amplifies cough-reflex sensitivity. OBJECTIVES: To examine cough-reflex sensitivity in an experimental animal model. METHODS: We developed an experimental guinea pig model in which airway collapse similar to that in cough was induced by rapid negative pressure applied to the airway of artificially ventilated animals. We examined the influence of this stimulus on cough-reflex sensitivity to inhaled capsaicin and bronchoalveolar lavage (BAL) cell components. After the termination of artificial ventilation, the number of coughs due to capsaicin was measured, and BAL was performed. MEASUREMENTS AND MAIN RESULTS: Capsaicin cough-reflex sensitivity and the number of BAL neutrophils were increased 6 hours after stimulus application, decreasing to control levels by 24 hours. Cough-reflex sensitivity or BAL cell components were not changed in the absence of stimulus application. The number of BAL neutrophils correlated significantly with the number of coughs. Hydroxyurea inhibited the stimulus-induced increase in the number of coughs and airway neutrophil accumulation. CONCLUSIONS: Our findings suggest that cough itself is a traumatic mechanical stress to the airway wall that induces neutrophilic airway inflammation and cough-reflex hypersensitivity. Cough stress to the airway wall results in a self-perpetuating cough-reflex cycle.

Systemic capillary leak syndrome associated with compartment syndrome.

Systemic capillary leak syndrome is characterized by recurrent hypovolemic shock attributable to increased systemic capillary leakage. A 26-year-old woman was admitted because of recurrent episodes of hypovolemic shock. Hemoconcentration, hypoalbuminemia, and monoclonal gammopathy were observed. We diagnosed systemic capillary leak syndrome. Three years later, she again had an attack of systemic capillary leak syndrome complicated with pretibial compartment syndrome. This case emphasizes the importance of muscle compartment pressure monitoring during volume resuscitation in patients with systemic capillary leak syndrome.

A phase II study of combination chemotherapy with docetaxel and carboplatin for patients with advanced or metastatic non-small cell lung cancer.

BACKGROUND: The aim of this phase II study was to evaluate the efficacy of combination chemotherapy consisting of docetaxel and carboplatin in patients with inoperable non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: For this multicenter phase II study, the eligibility criteria included histologically or cytologically proven inoperable NSCLC, measurable lesions, Eastern Cooperative Oncology Group performance status (PS) 0-2, adequate organ and bone marrow functions, and written informed consent. Patients received 60 mg/m2 of docetaxel and carboplatin (target AUC 5.5) on day 1 every 3 weeks until disease progression. The primary end-point of this study was response rate and the secondary end-points were toxicities, time to progression and overall survival. RESULTS: A total of 40 patients were enrolled and 39 patients were eligible. A complete response and partial response were observed in 1 and 13 patients, respectively. An objective response rate was 35.9% (95% confidential interval [CI] 20.8-51.0%). The median time to progression was 5.2 months and the median overall survival was 12.0 months. The 1- and 2-year survival rates were 53.8% and 25.1%, respectively. The major toxicities were leukocytopenia and neutropenia. Grade 3 or 4 thrombocytopenia was rare and non-hematological toxicities were generally mild. Grade 3 non-hematological toxicities were observed in 6 patients (2 with nausea and vomiting, 1 with diarrhea, 1 with elevated transaminase levels, 1 with allergic reaction and 1 with edema). No grade 4 non-hematological toxicities were observed. CONCLUSION: Docetaxel and carboplatin combination chemotherapy was well tolerated and active in Japanese patients with advanced or metastatic NSCLC.