[Two cases of refractory asthma presenting chest pain, which were successfully treated with noninvasive positive pressure ventilation].

We report here two cases of refractory asthma presenting chest pain, which were successfully treated by using intermittent noninvasive positive pressure ventilation (NPPV). Both patients were women, and were diagnosed to have bronchial asthma with the reversibility of airway contraction after administration of a bronchodilator. Although both patients were treated with several medicines for "treatment step 4" based on the guideline in Japan, their asthma could not be controlled well and their symptoms including the chest pain eroded their quality of life. We tried to use NPPV for 30 minutes in our clinic, and their symptoms improved. Therefore, we innovated for them intermittent NPPV as a home treatment. After 3 to 5 months, their asthma, including the symptom of chest pain, improved. In addition, pulmonary function tests revealed stable vital capacity and forced expiratory volume in 1 second in all cases after the NPPV therapy, while V50 and V25 were improved. These results suggest that NPPV may be a useful treatment option for patients with refractory asthma, especially those presenting chest pain.

Inhibitory effects of pitavastatin on fibrogenic mediator production by human lung fibroblasts.

AIMS: Idiopathic pulmonary fibrosis continues to be a devastating clinical disorder for which there are few therapeutic options, and the pathogenesis of this disease remains largely unknown. Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in cholesterol biosynthesis, and they have been reported to exert pleiotropic effects on the cellular signaling involved in tissue inflammation and in organ fibrosis/remodeling. We examined the preventive effects of statins on fibrogenic mediator expression and production in normal human lung fibroblasts (NHLF). MAIN METHODS: NHLF were pretreated with 100nM pitavastatin or medium alone (control), and were then stimulated with transforming growth factor-ß1 (TGF-ß1). mRNA expression and protein secretion of several mediators from cells were analyzed by real-time polymerase chain reaction, enzyme-linked immunosorbent assay or multiplex assay. KEY FINDINGS: TGF-ß1-induced expression or production of mediators, such as collagen-1, vascular endothelial growth factor and chemokine C-X-C motif ligand 8, in NHLF pretreated with pitavastatin was significantly suppressed with inhibition of Smad-3 phosphorylation, as compared to untreated controls. In addition, the inhibitory effects of pitavastatin were negated by addition of mevalonate. SIGNIFICANCE: Pitavastatin appeared to inhibit TGF-ß1-induced fibrogenic mediator production from lung fibroblasts via the mevalonic cascade. Although further evaluation of the signaling pathways for these phenomena is necessary, our results suggest the potential benefits of pitavastatin.

Protocol-based noninvasive positive pressure ventilation for acute respiratory failure.

PURPOSE: Noninvasive positive pressure ventilation (NPPV) has been suggested to be associated with adverse outcomes in emergency patients with acute respiratory failure (ARF), possibly because of a delay in tracheal intubation (TI). We hypothesized that protocol-based NPPV (pNPPV) might improve the outcomes, compared with individual physician-directed NPPV (iNPPV). METHODS: To guide decision making regarding the use of NPPV, we developed an NPPV protocol. Observational data were collected before and after protocol implementation in consecutive patients with ARF and compared between the pNPPV and the iNPPV groups. RESULTS: The results for pNPPV (n = 37) were compared with those for iNPPV (n = 37). No significant baseline differences in patient characteristics were observed between the two groups except for mean age, which was higher in the pNPPV group than in the iNPPV group (P = 0.02). Rate of TI and duration of mechanical ventilation were similar in the two groups. However, the time from the start of NPPV until TI tended to be shorter in the pNPPV group than in the iNPPV group (P = 0.11). The hospital mortality rate was significantly lower in the pNPPV group than in the iNPPV group (P = 0.049). Although the length of hospital stay was shorter in the pNPPV group than in the iNPPV group, this trend did not reach statistical significance (P = 0.14). CONCLUSIONS: The present study suggests that pNPPV is effective and likely to improve the mortality rate of emergency patients with ARF.

[A case of hepatopulmonary syndrome with elevated exhaled nitric oxide].

A 76-year-old man was admitted to our hospital because of dyspnea. Three years before admission, dyspnea was recognized and had been given a diagnosis of interstitial pneumonia by a general physician. A year later, he received home oxygen therapy. After admission, we found that he had alcoholic liver cirrhosis and an increased alveolar-arterial oxygen level in his arterial blood gas. Moreover, he had an intrapulmonary vascular shunt, detected by contrast-enhanced echocardiography and perfusion scan with 99mTc-macroaggregated albumin. These results confirmed hepatopulmonary syndrome. Furthermore, exhaled nitric oxide (NO) was elevated in the patient although he had never had bronchial asthma or any other allergic diseases. Animal models of hepatopulmonary syndrome have shown that exhaled NO is associated with dilated vessels. To the best of our knowledge, this paper describes the first case of hepatopulmonary syndrome with elevated exhaled NO in Japan.