Clinical application of ghrelin for chronic respiratory failure.

Chronic respiratory failure, which is often caused by chronic obstructive pulmonary disease, chronic lower respiratory tract infection, or interstitial pneumonia, often leads to cachexia with disease progression. Patients who have chronic respiratory failure with cachexia exhibit increased morbidity. Although cachectic status is an important clinical problem, there are no effective therapies for cachexia. Ghrelin has various effects, including increasing food intake, attenuating sympathetic nerve activity, inhibiting inflammation, increasing cardiac output, and controlling fat utilization. These effects of ghrelin are ideal targets for the treatment of severely wasting chronic respiratory disease. In a few clinical studies, including a small randomized controlled trial, ghrelin administration to cachectic patients with chronic respiratory failure improved exercise tolerance, dyspnea, and appetite. The patients in these studies gained muscle mass and weight. In another study of chronic lower respiratory tract infection with cachexia, ghrelin suppressed airway inflammation by decreasing neutrophil accumulation in the airway, resulting in improvements in oxygenation and exercise tolerance. Although further clinical investigations are needed to clarify its usefulness, ghrelin is expected to become a novel therapy for cachectic patients with chronic respiratory failure.

Ghrelin administration for chronic respiratory failure: a randomized dose-comparison trial.

BACKGROUND: Repeated ghrelin administration leads to improvements in symptoms, muscle wasting and exercise tolerance in cachectic patients with pulmonary disease. We investigated the optimal ghrelin dose for underweight patients with chronic respiratory failure. METHODS: In this multicenter, randomized, dose-comparison exploratory study, 44 cachectic patients with chronic respiratory failure were randomly assigned pulmonary rehabilitation with intravenous twice-daily administration of 1 or 2 µg/kg ghrelin for 3 weeks. The primary endpoint was improvement in 6-min walking distance (6 MWD). The secondary endpoint was change in peak VO2. RESULTS: Twenty-one patients were assigned to the 1 µg/kg ghrelin group and 23 to the 2 µg/kg ghrelin group. Change from baseline 6 MWD after treatment was similar between groups(1 µg/kg: 53.9 m, 2 µg/kg: 53.9 m, p = 0.99). Mean change in peak VO2 was significantly greater in the 2 µg/kg group (63.1 ml/min) than in the 1 µg/kg group (-63.8 ml/min, p = 0.048). Food intake and lean body mass significantly increased in both groups, and the St. George Respiratory Questionnaire score, body weight, and body mass index were remarkably improved in only the 2 µg/kg group, although there was no significant difference between groups. No treatment-related serious events were reported for either group. CONCLUSION: Improvements in the oxygen uptake capacity were greater in patients receiving 2 µg/kg ghrelin twice daily for 3 weeks than in those receiving 1 µg/kg, although exercise tolerance was similar between groups at the end of the 3-week treatment period. Thus, a twice daily dose of 2 µg/kg ghrelin is recommended over 1 µg/kg ghrelin for patients with chronic respiratory failure and weight loss.

Long-term treatment with theophylline reduces neutrophils, interleukin-8 and tumor necrosis factor-alpha in the sputum of patients with chronic obstructive pulmonary disease.

BACKGROUND: The non-selective phosphodiesterase inhibitor theophylline has bronchodilator/anti-inflammatory properties and is widely used in the treatment of airways diseases. We determined the effect of long-term theophylline treatment on airway inflammation in patients with chronic obstructive pulmonary disease (COPD). POPULATIONS AND METHODS: Seventeen stable COPD patients were enrolled in the 12-month study. Theophylline was administered at 400mg/day. We studied changes in symptoms, spirometry, sputum volume, and sputum inflammatory cytokines levels. We also examined the effects of theophylline on the release of inflammatory cytokines in vitro by measuring interleukin (IL)-8 and tumor necrosis factor (TNF)-alpha levels from lipopolysaccharide (LPS)-stimulated neutrophils and THP-1 cells. RESULTS: Forced vital capacity was increased and sputum IL-8 levels decreased after 4 weeks of theophylline treatment. After 6 months of theophylline treatment, forced expiratory volume in 1s was increased, and neutrophils counts and TNF-alpha levels in sputum were reduced. Levels of IL-8 and TNF-alpha released by LPS-stimulated THP-1 cells were reduced by treatment with theophylline at 10microg/ml. In contrast, IL-8 levels released by LPS-stimulated neutrophils were reduced by treatment with theophylline at 100microg/ml. CONCLUSION: Our clinical study of small population showed that long-term treatment with theophylline seems to reduce airway inflammation in stable COPD patients.

[A case of paragonimiasis westermani with a worm migration track on chest CT].

A 59-year-old man with rusty-colored sputum was admitted for evaluation of a nodular shadow on his chest radiograph. Chest computed tomography (CT) revealed nodules and nodular opacities with a cavity in the right S3. Chest CT also showed clearly a double linear shadow other than the bronchovascular bundle, with a different course from that of the bronchovascular bundle, suggesting a worm migration track. The diagnosis of paragonimiasis westermani was confirmed by detection of Paragonimus eggs in a bronchoscopic aspirate smear and by immunoserological examination. The linear lesion on the chest CT is uncommon in paragonimiasis, but the finding is thought to be useful for the diagnosis of this disease.

Acute eosinophilic pneumonia with fine nodular shadows.

A 19-year-old woman presented with acute onset of cough and dyspnea. She started smoking two weeks before the appearance of symptoms. On admission, arterial blood gas analysis on room air breathing revealed PaO2 55 Torr. Chest roentgenogram and high resolution computed tomograms showed localized fine nodular shadows at the right lower lung field. Bronchoalveolar lavage fluid revealed a high eosinophil count. Eosinophil infiltration was also observed in transbronchial lung biopsy specimens. The final diagnosis was acute eosinophilic pneumonia (AEP). Although few reports have demonstrated diffuse fine nodular shadows in AEP, localized fine nodular shadows on chest roentgenogram and CT may sometimes be the sign of AEP especially in the early phase of the clinical course.

A case of non-small cell lung cancer with false-positive staging by positron emission tomography.

A 70-year-old woman with right lung cancer was admitted to our hospital. Chest computed tomography (CT) revealed an approximate 2.5 cm sized mass in the right middle lobe, and enlarged hilar and mediastinal lymph nodes. The 2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) showed high uptake in the right hilar and mediastinal nodes. Therefore we diagnosed N2 (mediastinal nodal involvement) disease. Microscopically, however, all dissected lymph nodes revealed anthracosilicosis and negative for malignancy. Although false-positive evaluation of mediastinal involvement by PET can occur in the setting of metabolically active inflammatory disease, this case did not have these active diseases. The FDG-PET result of this case was unusual.