Proton Pump Inhibitor Improves Breath Marker in Moderate Asthma with Gastroesophageal Reflux Disease

Shimizu, Yasuo; Dobashi, Kunio; Zhao, Jian; Kawata, Takefumi; Ono, Akiko; Yanagitani, Noriko; Kaira, Kyoichi; Utsugi, Mitsuyoshi; Hisada, Takeshi; Ishizuka, Tamotsu; Mori, Masataka

doi:10.1159/000101437

Cited by 31 publications

(43 citation statements)

References 56 publications

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“…In a study of patients with moderate asthma, the EBC 8-isoprostane levels of patients with GERD were higher than those of patients without GERD, and the EBC 8-isoprostane level of patients who had moderate asthma accompanied by GERD was improved by high-dose treatment with proton pump inhibitors. It was also reported that the decrease of EBC 8-isoprostane was accompanied by improvement of asthma symptoms [10]. Based on the above findings, it is speculated that the 8-isoprostane level of EBC reflects airway inflammation due to GERD as well as causing exacerbation of asthma.…”

Section: Analysis Of Ebcmentioning

confidence: 79%

“…Since 8-isoprostane levels increase when asthma is more severe or due to acute exacerbation, further consideration may be needed as to whether it can serve as a marker of GERD complications. The clinical relevances of EBC pH to pulmonary disease with GERD are that reduced pH reflects GERD severity evaluated by questionnaire in COPD [12], and improved pH is observed proton pump inhibitor (PPI) response in asthma with GERD [10]. EBC pH is reproducible and reflects a significant part of asthma pathophysiology [13].…”

Section: Analysis Of Ebcmentioning

confidence: 99%

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Assessment of Airway Inflammation by Exhaled Breath Condensate and Impedance Due to Gastroesophageal Reflux Disease (GERD)

Shimizu¹,

Dobashi²,

Nagoshi³

et al. 2009

IADT

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Avoiding oxidative stress in the airways is important for the treatment of respiratory disease associated with gastroesophageal reflux disease (GERD). It is often difficult to decide whether GERD is causing airway inflammation or whether an airway disease is complicated by GERD. Measurement of exhaled breath condensate (EBC) is performed by cooling and collecting the airway lining fluid contained in exhaled air. A decrease of pH and an increase of the 8-isoprostane concentration in EBC have been observed in patients with mild to moderate asthma accompanied by GERD. There are still problems to be overcome before EBC can be used clinically, but pH and 8-isoprostane may be promising objective markers of airway inflammation due to GERD. The disease concept and diagnosis of GERD are constantly advancing, including the development of impedance methods. It is expected that treatment will be based on the latest diagnostic knowledge of GERD associated with respiratory disease and on monitoring of airway inflammation.

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Section: Analysis Of Ebcmentioning

confidence: 79%

Section: Analysis Of Ebcmentioning

confidence: 99%

Assessment of Airway Inflammation by Exhaled Breath Condensate and Impedance Due to Gastroesophageal Reflux Disease (GERD)

Shimizu¹,

Dobashi²,

Nagoshi³

et al. 2009

IADT

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“…The 8-isoPGF 2a concentrations were measured by using a specific enzyme immunoassay kit (Cayman Chemical, Mich, USA), as reported previously (24).…”

Section: Measurement Of8-isopgf 2a In Ebcmentioning

confidence: 99%

Rock Activation in Lung of Idiopathic Pulmonary Fibrosis with Oxidative Stress

Shimizu

Dobashi

Sano

et al. 2014

Int J Immunopathol Pharmacol

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The Rho-associated coiled-coil containing protein kinase, (Rho-kinase or ROCK) undergoes activation by oxidative stress. ROCK-II, which is an isoform of ROCK, is activated in a murine model of lung fibrosis. The present study evaluated the level of oxidative stress and activation of ROCK-II in patients with idiopathic pulmonary fibrosis (IPF). The ROCK-II level and the phosphorylation of myosin phosphatase subunit-1 (p-MYPT-1), a hallmark of ROCK activation, were examined by immunohistochemistry of lung tissue sections. The 8-iso prostaglandin-F2α (8-isoPGF2α) level, as a marker of oxidative stress, of exhaled breath condensate was significantly higher in IPF patients than in control patients. In IPF lungs, ROCK-II was predominantly expressed by bronchial epithelial cells, as well as at a lower level by airway smooth muscle cells, vascular smooth muscle cells, and the fibroblasts of fibroblastic foci (FF). In addition, there was moderate p-MYPT-1 expression in these cells of IPF lungs. In control lungs, ROCK-II was expessed by these cells. p-MYPT-1 was weakly expressed by the bronchial epithelial cells. In conclusion, ROCK-II was activated in various lung cells of IPF patients along with oxidative stress detected by 8-isoPGF2α elevation. The ROCK pathway may play a role in the development of IPF via oxidative stress.

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“…The hypothesis that reflux of gastric content into the airway may cause interstitial fibrosis has been proposed by several investigators in experimental models and in other diseases [15,16,17,18,19,20,21]. …”

Section: Introductionmentioning

confidence: 99%

Centrilobular Fibrosis: An Underrecognized Pattern in Systemic Sclerosis

Souza¹,

Borges²,

Capelozzi³

et al. 2008

Respiration

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Background: The impressive association of lung involvement and gastroesophageal reflux in scleroderma raises the possibility of a cause-effect relationship. Objectives: To determine clinical, radiological and histopathological features of systemic sclerosis (SSc) patients according the presence or absence of centrilobular fibrosis (CLF). Methods: Twenty-eight SSc patients with lung involvement were submitted to open lung biopsy and the specimens classified for the presence of CLF (bronchocentric distribution of the lesions and intraluminal matter according to the classification of idiopathic interstitial pneumonia). HRCT, pulmonary function tests and esophageal analysis were also performed. Subsequently, cyclophosphamide was introduced for the nonspecific interstitial pneumonia subgroup and antireflux treatment was intensified for isolated CLF patients. Results: Isolated CLF was found in 21% of the biopsies and also found associated to nonspecific interstitial pneumonia in 84% of these patients. The other 3 cases had usual interstitial pneumonia, pulmonary hypertension and respiratory bronchiolitis-associated interstitial lung disease. The histopathological analysis revealed that all 6 patients with isolated CLF had the bronchocentric distribution and intraluminal basophilic content, with foreign bodies detected in one third of them. The central distribution of lung involvement on HRCT was found in 67% of these patients with a consistent patchy distribution (100%). Ground glass (67%) and consolidation (33%) were the predominant patterns found. The constant clinical finding in all isolated CLF cases was dyspnea, esophageal abnormalities and a moderate lung impairment (FVC: 63.83 ± 16.31%; DLCO: 61.66 ± 18.84%). Lung function parameters in isolated CLF patients remained stable after 1 year of exclusively intensive antireflux treatment (FVC, p = 0.23; DLCO, p = 0.59). Conclusions: The novel description of CLF pattern in SSc lung disease with peculiar histological, tomographic and clinical features will certainly contribute to a more appropriate therapeutic approach.

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Proton Pump Inhibitor Improves Breath Marker in Moderate Asthma with Gastroesophageal Reflux Disease

Cited by 31 publications

References 56 publications

Assessment of Airway Inflammation by Exhaled Breath Condensate and Impedance Due to Gastroesophageal Reflux Disease (GERD)

Assessment of Airway Inflammation by Exhaled Breath Condensate and Impedance Due to Gastroesophageal Reflux Disease (GERD)

Rock Activation in Lung of Idiopathic Pulmonary Fibrosis with Oxidative Stress

Centrilobular Fibrosis: An Underrecognized Pattern in Systemic Sclerosis

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