No abstract

Background -The precise mechanism of high altitude pulmonary oedema (HAPE) remains unclear. The purpose ofthis study was to evaluate the role of cytokines and P-selectin in the development of HAPE which occurred at moderate altitude in Japan. Methods -The following cellular and biochemical markers and chemotactic cytokines were measured in the bronchoalveolar (BAL) fluid from four patients with HAPE at 2857-3180 m in the Japanese Alps: total proteins, albumin, lactate dehydrogenase (LDH), and interleukin (IL)-la, IL-1p, IL-1 receptor antagonist (ra), IL-6, IL-8, IL-10, tumour necrosis factor (TNF)-a, and the soluble form of Pselectin. Results -At admission there were significant increases in the levels oftotal cells, especially macrophages and neutrophils, total protein, albumin and LDH when compared with 13 healthy individuals.Furthermore, the levels of IL-1p, , and TNF-a were also considerably increased but returned quickly to the normal ranges or were not detected after recovery. The levels of IL-la, IL-10, and P-selectin did not change. Conclusions -These results suggest that an inflammatory process almost identical with acute respiratory distress syndrome (ARDS) may occur in HAPE, but that these changes are transient and are not associated with any increase in P-selectin levels in the BAL fluid. (Thorax 1996;51:739-742) Keywords: cytokines, bronchoalveolar lavage, high altitude pulmonary oedema.High altitude pulmonary oedema (HAPE) is a non-cardiogenic pulmonary oedema that occurs in healthy individuals and is seen among those ascending above 2700 m in the Japanese Alps.' Its precise mechanism remains unresolved. Although the oedema formation of HAPE might be related to the shear forces associated with increased pulmonary vascular pressure," it is mainly due to increased pulmonary permeability.4 Conversely, recent studies5-7 of the pathophysiology of adult (or acute) respiratory distress syndrome (ARDS) or acute lung injury, a pulmonary oedema with typically increasing permeability, have revealed that ARDS is characterised by a significant inflammatory component followed by infiltration of mainly neutrophils and macrophages. There are many studies of chemical mediators, chemical cytokines, and adhesion molecules in the bronchoalveolar lavage (BAL) fluid of patients with ARDS.5-7 Sakamaki et al have recently reported that the level of the soluble form of P-selectin is increased in the plasma of patients with ARDS. From its clinical characteristics it is possible that HAPE is one form of acute lung injury, but no data are available concerning these mediators in HAPE. We have measured the levels of chemotactic cytokines and Pselectin in the BAL fluid ofpatients with HAPE in order to evaluate the role of these mediators in the development of HAPE. Methods PATIENTSWe examined the cellular and biochemical markers and the chemical cytokines in the BAL fluid of four men with HAPE who were admitted to Shinshu University Hospital (600 m above sea level) which is located at the foot of the Japanese Alps. Al...

We tried to characterize the clinical features and findings on chest high resolution computed tomography (HRCT) of patients with Mycobacterium avium-intracellulare (MAI) pulmonary infection without known predisposing lung disease and with no immunodeficiency. We also aimed to clarify the small airway and alveolar inflammation using bronchoalveolar lavage (BAL) from the affected regions. MAI infection was diagnosed in 53 patients from respiratory samples, including sputum and materials obtained using a fiberoptic bronchoscope. None had a predisposing lung disease or immunodeficiency, as assessed by medical history, routine laboratory data, and previously normal chest radiographs and/or CT scans. The mean age of the 53 patients was 60 +/- 11 years, and 48 were nonsmoking females. They had few respiratory symptoms, although 42% had chronic paranasal sinusitis. Chest HRCT findings showed centrilobular small nodules and ectasia of small bronchi and/or bronchioles located mainly in segment (S) 2, 3, 4, and 5. S1, which is usually affected by pulmonary tuberculosis, was completely free of these opacities. The BAL study revealed that the predominant cells were activated T lymphocytes and neutrophils. The CD4+/CD8+ ratio increased significantly. Bacteriology was negative for other bacteria and fungi. Although our patients did not present with distinct respiratory symptoms, the regions affected by MAI showed a chronic inflammation of mainly neutrophils and activated T lymphocytes. The presence of chronic sinusitis may be merely coincidental. However, its high prevalence and the finding of bronchiectasis in chest HRCT raise the question of whether silent bronchiectasis may be a predisposition.

Background -Hepatitis C virus (HCV) infection has recently been incriminated as an aetiological agent in idiopathic pulmonary fibrosis. This study was performed to determine the cellularity and lymphocyte phenotypes ofbronchoalveolar lavage (BAL) fluid in patients with chronic hepatitis C. Methods -BAL fluid and lavage lymphocyte subsets from 13 patients (10 men) with active chronic hepatitis C, diagnosed by sustained elevated serum glutamic pyruvic transaminase and typical histological findings in the liver, were analysed. Lavage findings in these patients were compared with those from 13 healthy volunteers (eight men) as controls. To elucidate whether HCV infection is related to the pathogenesis ofIPF, we investigated the cellularity and lymphocyte phenotypes of bronchoalveolar lavage (BAL) fluid, and performed pulmonary function tests in patients with chronic hepatitis C. Methods SUBJECTSThirteen patients (10 men) of median age 57 years (range 31-64) with chronic hepatitis C proven by the typical histological findings observed within the previous six months and the presence of sustained elevated serum levels of glutamic pyruvic transaminase (GPT) for at least six months were studied. All patients were positive for antibody to HCV in serum and negative for hepatitis B surface antigen. They were treated with interferon after this study. The following patients were excluded from the study: those who had received a course of antiviral or immunosuppresive therapy which may lead to alveolitis within six months; those who had a positive titre for autoantibodies to collagen diseases; those who exhibited leucopenia (<3000/ml) and thrombopenia (<80 000/ml). None of the patients had a familial history of IPF and none had pulmonary fibrosis as determined from symptoms, physical signs, and radiographic findings. Thirteen healthy volunteers (eight men) of median age 49 years (range 24-67) acted as controls.Subjects in both groups were defined as smokers if they currently smoked cigarettes and ex-smokers if they had not smoked within the preceding six months. This study was performed according to the criteria of the Helsinki Declaration and free and informed consent was obtained from all patients and normal volunteers.BRONCHOALVEOLAR LAVAGE (BAL) Subcutaneous injections of atropine (0 5 mg) and pethidine hydrochloride (0 5 mg/kg) were given. The oral pharynx and upper airway was anaesthetised with 2% lignocaine (lidocaine).

Conclusion: These results suggest that gefitinib readministration may be an opti on, albeit with a low response rate and short progression-free survival, for patients 4 who responded well to initial gefitinib followed by systemic chemotherapy. These findings provide valuable in formation for the management of previous gefitinib responders.