Analysis of the contributing factors to airway hyperresponsiveness by a forced oscillation technique in patients with asthma.

BACKGROUND: Forced oscillation technique (FOT) is increasingly used to obtain much information on the state of the respiratory system. However, there are little data about FOT parameters on methacholine provocation test in adult asthma. This study was designed to determine the physiological implications of FOT parameters during methacholine provocation and analyze the major contributing factors to airway hyperresponsiveness (AHR) in asthma. METHODS: Spirometry and FOT were performed in 22 asthmatic patients and 21 normal control subjects before and after provocation with a maximal dose of methacholine. RESULTS: In asthmatic patients, the percent increase in resistance at 5 Hz (R5) and resistance at 20 Hz (R20) after the methacholine provocation was 70 [45-93] % and 16 [5-23] %. The percent change in R20 was not significantly correlated with the percent change in FVC or FEV1. Similarly, the percent change in R5 was not significantly correlated with the percent change in FEV1, but was significantly correlated with the percent change in FVC. Moreover, the percent change in R5 was significantly correlated with the closing index (r = 0.55, p = 0.01). In addition, AHR to methacholine was closely correlated with the percent change in R5 (r = -0.71, p = 0.001). CONCLUSIONS: Simultaneous measurement of FOT and bronchial challenge test provide meaningful information, and greater change in R5 may represent exaggerated response of small airways in asthmatic patients. This study will provide new insights into the physiological implications of each FOT parameter in asthmatic patients.

Association of airway pentosidine levels with bronchodilator response mediated by salbutamol administration in asthmatic patients.

BACKGROUND: Recently, increased levels of pentosidine, an intermolecular cross-linking type of advanced glycation end products, are observed in the airways of asthmatic patients. This study was designed to determine whether differences in bronchodilator response among individuals with asthma are attributable to pentosidine levels in their airways. METHODS: Fifty-six asthmatic patients (21 with airway obstruction, 35 without airway obstruction) and 10 normal controls were included in this study. For asthmatic patients, we evaluated the spontaneous reversibility of airway obstruction or the reversibility that can be obtained after methacholine provocation. And we also measured pentosidine levels and percentage of sputum eosinophils in induced sputum, and exhaled nitric oxide (NO) levels. RESULTS: The pentosidine levels did not significantly differ between the two asthmatic subgroups with and without airway obstruction. In asthmatic patients without airway obstruction, airway hyperresponsiveness to methacholine (PC20 methacholine) was significantly correlated with sputum eosinophils and exhaled NO levels. In contrast, PC20 methacholine was not significantly correlated with pentosidine levels. In asthmatic patients with or without airway obstruction, bronchodilator response was not significantly correlated with sputum eosinophils and exhaled NO levels. However, bronchodilator response was closely correlated with pentosidine levels (asthmatics without airway obstruction: r = -0.54, p = 0.002; asthmatics with airway obstruction: r = -0.48, p = 0.03). CONCLUSIONS: Our results showed that pentosidine might be a potential biomarker reflecting the reduced bronchodilator response in asthma. This study will provide new insights into the mechanisms underlying persistent airway obstruction.

[A case of drug-induced pneumonia caused by clopidogrel].

A 65-year-old man, who had been given a diagnosis of angina pectoris, developed pneumonia 6 months after the initiation of clopidogrel to inhibit platelet aggregation. Chest radiography showed bilateral invasive shadows, and he was admitted to our hospital. He was asymptomatic, but his C-reactive protein and erythrocyte sedimentation rate were elevated. A lymphocyte stimulation test (DLST) with clopidogrel was positive, and bronchoalveolar lavage fluid showed an increase in lymphocytes and a decrease in the CD4+/CD8+ ratio. We noticed no radiologic improvement a week after prednisolone therapy (30 mg/day) with clopidogrel as stated. However, the airspace consolidation had slightly reduced after clopidogrel was halted. We found a few cases of ticlopidine-induced pneumonia, in the literature, but we found no cases of pulmonary adverse events caused by clopidogrel. To the best of our knowledge this is the first case of clopidogrel-induced pneumonia.

An isolated der(1;21)(q10;q10) translocation in a patient with myelodysplastic syndrome: a case report.

Whole-arm translocations are relatively rare among hematological malignancies. There are a few reports on myeloid malignancies harboring der(1;21)(q10;q10). A 65-year-old male was referred to our hospital due to squamous cell carcinoma of the lung. Pembrolizumab monotherapy resulted in progression, and so chemotherapy involving nab-paclitaxel and carboplatin was administered thereafter. The patient developed cytopenia, and his bone marrow exhibited dysplasia. Chromosomal analysis revealed a whole-arm translocation, der(1;21)(q10;q10). Thus, the patient was diagnosed with myelodysplastic syndrome. The der(1;21)(q10;q10) translocation is a rare variant of the der(1;7)(q10;p10) translocation, which is an adverse prognostic factor for myeloid neoplasms. Clarifying the clinical features of myeloid neoplasms in patients with der(1;21)(q10;q10) would facilitate the elucidation of their tumorigenic mechanisms.