Sequential Granulocyte-Macrophage Colony-Stimulating Factor Inhalation after Whole-Lung Lavage for Pulmonary Alveolar Proteinosis. A Report of Five Intractable Cases.

Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by the excessive accumulation of surfactant proteins within the alveolar spaces and by higher titers of autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) in the serum and bronchoalveolar lavage fluid. The antibodies inhibit the maturation and phagocytosis of alveolar macrophages. Although the standard therapy for aPAP has been whole-lung lavage (WLL), this procedure is invasive and needs to be repeated for several years. GM-CSF inhalation therapy is a new procedure for treating aPAP and can induce remission with less invasiveness, although it is generally less effective in severe cases. We evaluated five cases with remarkable improvement by using sequential GM-CSF inhalation therapy after WLL; however, the treatment failed when this therapy preceded WLL. Therefore, sequential GM-CSF inhalation after WLL may reinforce the efficiency of WLL in patients with severe aPAP.

OMALIZUMAB RESCUED A ASTHMA-COPD OVERLAP SYNDROME PATIENT FROM A STATUS ASTHMATICS UNDER THE ICU MANAGEMENT.

An atopic asthmatic of 65-year-old man who was complicated with COPD and treated with inhaled corticosteroid, long-acting ß2 agonist, long-acting muscarinic antagonist, and leukotriene receptor antagonist was hospitalized with a severe asthmatic attack. He was intubated and went onto an artificial respirator. He was gradually relieved by repeated intravenous administration of high-dose corticosteroid, and a respirator was switched over to non-invasive positive pressure ventilation on 24th day. However, he repeated asthmatic attacks which needed corticosteroid to recover. Omalizumab was administered on 35th day and asthmatic attacks remarkably decreased. He left the hospital on 71st day. It was thought that the additional administration of omalizumab provided a good clinical response for an intractable asthma.

[A case of lung injury induced by long-term administration of mesalazine].

A 52-year-old man was given a diagnosis of ulcerative colitis and treated with mesalazine for 7.5 years. However, the unusually long administration of mesalazine induced lung injury and the patient complained of a dry cough and dyspnea on limited exertion. Infiltrative shadows were observed in bilateral lung fields on a chest radiograph and computed tomographic images. The histological findings obtained by transbronchial biopsy and bronchoalveolar lavage showed organizing pneumonia. His drug-induced lymphocyte stimulation test (DLST) for mesalazine was positive. Improvements in his clinical symptoms and radiographic abnormalities occurred spontaneously after the discontinuation of mesalazine. This case indicates that the long-term administration of mesalazine may lead to an adverse pulmonary reaction.

A novel needle-type sampling device for flexible ultrathin bronchoscopy.

Diagnosis of suspected cancer in the periphery of the lung is difficult. A flexible ultrathin bronchoscope has been developed for the diagnosis of peripherally located pulmonary lesions that cannot be reached with the sampling devices for standard flexible bronchoscopes. The diagnostic yield with forceps and a brush for ultrathin bronchoscopes, however, is not adequate, especially when a lesion is not exposed to the bronchial lumen. We have thus developed a novel needle-type sampling device and tested its yield in transbronchial cytology. The device consists of an elongated dental H-file (0.4 mm in diameter and 110 cm in length), a housing sheath (1.0 mm in outer diameter), and a novel handle, which enables rapid out-and-in motion of the needle. Ten consecutive patients with a peripheral pulmonary lesion who had an indication for diagnostic procedure with a flexible ultrathin bronchoscope were enrolled. The optimal bronchial route to the lesion was analyzed with virtual bronchoscopy in a data set obtained with high-resolution computed tomography, and a novel bronchial route labeling system (prior-ridge-based relative orientation nomenclature) was employed to guide insertion of the bronchoscope. Sampling with the novel needle was performed prior to use of the forceps and brush under conventional fluoroscopy. In all the cases, sampling with the needle was successful and the amount of the specimen was sufficient for cytology. Our novel sampling system with flexible ultrathin bronchoscopes may contribute to accurate and minimally invasive diagnosis of peripheral pulmonary lesions.

Efficacy and safety of formoterol in Japanese patients with COPD.

OBJECTIVE: This study evaluated the efficacy and safety of the formoterol Turbuhaler at dosages of 4.5, 9 and 18 microg bid compared with placebo in Japanese patients with COPD. METHODS: In this randomized, double-blind, placebo-controlled, multicenter study, 36 patients with a pre-bronchodilator FEV(1) value within 40 to 70% of the predicted value were randomized to receive formoterol at doses of 4.5, 9, and 18 microg bid, and placebo, for 1 week in a crossover fashion. RESULTS: The primary outcome variable, one hour post-dose FEV(1) on the last day of the one week treatment period, was significantly higher for all formoterol dosages compared with placebo (p<0.001 for all doses); adjusted g-means for formoterol 4.5, 9 and 18 microg bid, and placebo, were 1.510 L, 1.491 L, 1.520 L and 1.342 L, respectively. All three dosages of formoterol also provided significantly better improvements than placebo in the secondary variables FVC, inspiratory capacity (IC) and morning and evening PEF. Results for IC and PEF indicated a trend towards a larger improvement at higher dosages. CONCLUSION: Treatment with formoterol at dosages of 4.5, 9 and 18 microg bid showed significantly superior effects to placebo on FEV(1) in Japanese patients with COPD. The results for some of the secondary variables (IC and PEF) indicated a trend towards larger improvements at higher dosages. All dosages of formoterol were well tolerated in Japanese patients.