Treatment of silicosis with hepatocyte growth factor-modified autologous bone marrow stromal cells: a non-randomized study with follow-up.

Pulmonary silicosis is an irreversible and untreatable disease that is characterized by interstitial lesions and perpetual fibrosis in the lungs. This study was performed to determine whether mesenchymal stem cells (MSCs) and hepatocyte growth factor (HGF) could exhibit therapeutic effects on human silicosis. This non-randomized uncontrolled trial comprised four patients with pulmonary silicosis who had developed lung fibrosis and received autologous bone marrow MSCs previously transfected by a vector containing human HGF cDNA (MSCs/HGF). MSCs/HGF were intravenously administered weekly for three consecutive weeks at a dose of 2 x 10(6) cells/kg. Pulmonary function, high kilo-voltage chest X-ray radiography, computed tomography (CT) scan, and peripheral blood lymphocyte subset and serum IgG concentrations were evaluated after cell therapy. The treatment was found to be generally safe. Symptoms such as cough and chest distress gradually ameliorated at six months post-therapy, accompanied by the significant improvement of pulmonary function. The ratios of the peripheral CD4- and CD8- positive cell concentrations were increased (P < 0.05). Furthermore, the serum IgG levels in these patients were decreased and reached the normal range (P < 0.05). CT scans showed partial absorption of the nodular and reticulonodular lesions in the lungs during follow-up of at least 12 months. The effectiveness of this novel regimen observed in these patients suggests that a placebo-controlled clinical trial needs to be developed. This study carries trial registration No. NCT01977131 (ClinicalTrials.gov).

Increased IL-35 serum levels in systemic sclerosis and association with pulmonary interstitial involvement.

The objective of this study is to assess the serum IL-35 level and its association with clinical manifestations in patients with systemic sclerosis (SSc). IL-35 serum levels were measured by ELISA from 56 patients with SSc and 53 healthy controls. Association of IL-35 serum levels were sought with clinical parameters. Serum IL-35 levels were significantly higher in SSc patients (5.08 ± 0.76 pg/ml) than in healthy individuals (1.89 ± 0.69 pg/ml; p < 0.0001). Patients with lung fibrosis had higher IL-35 levels than those without fibrosis (7.75 ± 1.36 and 3.08 ± 0.70 pg/ml, respectively, p = 0.0022). IL-35 is elevated in the serum of patients with SSc and is associated with lung fibrosis. Our findings suggest that this cytokine can have a role in fibrotic diseases, but further studies are needed to address the role of IL-35 in the pathogenesis of SSc.

Prevalence of high hematocrits in patients with interstitial lung disease in Mexico City.

Erythrocytosis, a known response to chronic hypoxemia, is considered infrequent in interstitial lung diseases. We studied the prevalence of high hematocrit (Hct) values and the relationship between Hct and SaO2 in 79 patients with chronic pigeon breeder's lung (PBL) and 34 with idiopathic pulmonary fibrosis (IPF), all of whom lived in the Mexico City metropolitan area (2,240 m above sea level). Lung biopsy was performed in 31 patients with IPF and 71 with PBL. We analyzed only one simultaneous measurement of Hct and SaO2 per patient (usually the initial measurement) before treatment. No additional cause for anemia or erythrocytosis was detected. Forty-eight percent of the patients with PBL (38/79) and 62 percent of those with IPF (21/34) had high Hct values (greater than 2 SD above mean values for Mexico City); in 14 (12.3 percent) of the 113 patients (nine with PBL and five with IPF), the Hct was above 60 percent. The Hct and SaO2 values displayed a poor correlation for the whole group: Hct = 65.7-0.16(SaO2), r = 0.24, p = 0.012. The correlation between Hct and SaO2 was nonsignificant if patients were separated by diagnosis. For an SaO2 of less than 80 percent, the slope of SaO2 vs Hct was zero. Half of our patients with PBL and IPF had Hct values that were high for the altitude. In most cases, Hct responses fell within the confidence limits reported as normal at high altitudes. We found a poor relationship between Hct and awake SaO2.

[Unilateral lung transplant in a case of terminal pulmonary fibrosis]. / Trasplante unilateral de pulmón en un caso de fibrosis pulmonar terminal.

Up to 1980, less than 40 lung transplants had been reported worldwide without any success. The factors influencing these poor results were related to complications at the bronchial anastomosis and ineffective immunosuppressive regimens. The development of new immunosuppressive drugs has permitted the reevaluation of lung transplantation as a therapeutic option. The success with heart-lung transplantation stimulated the development of clinical human single-lung and double-lung transplantation. However the world experience is still scarce. In our institution we have developed experimental work leading to the establishment of a lung transplant program. This paper describes our first single lung transplant patient. The patient, a 33 year old man with end-stage pulmonary fibrosis, was totally oxygen dependant, maintaining arterial blood oxygen levels below 40 mmHg without oxygen supplementation and confined to a wheelchair. A single left lung transplant was performed from a young brain-dead donor. The bronchial anastomosis was protected with an omental flap. The immunosuppressive regimen was based on cyclosporin A and azathioprine from the beginning, adding prednisone on the third postoperative week. There has been only one episode suggestive of acute rejection which was managed with methylprednisolone. On the 9th postoperative week the patient developed a bronchial stenoses at the anastomotic site which required dilation and stenting with an endobronchial silastic stent. His clinical course has been uneventful since then. His ventilatory parameters showed an increase of vital capacity from 900 to 2100 mL and his FEV1 from 700 to 1500 mL. His gas exchange has been normal with arterial blood gas oxygen above 60 mmHg and oxygen saturation above 94%.(ABSTRACT TRUNCATED AT 250 WORDS)

PaO2 increases with coughing in patients with chronic lung disease.

We considered if the cyanosis frequently observed during a cough attack in patients with chronic lung disease was due to worsening hypoxemia. To investigate the effects of cough on PaO2, we measured arterial blood gases before and after a voluntary coughing period of 45 sec, in 11 patients with Interstitial Lung Disease (ILD) and 14 patients with Chronic Obstructive Lung Disease (COPD). All patients significantly increased (p less than 0.05) their PaO2 (COPD: from 49 +/- 2 to 60 +/- 2 mmHg; ILD from 44 +/- 2 to 51 +/- 3 mmHg, mean +/- SD) and decreased their PaCO2. We conclude that stable patients with COPD and ILD increase their PaO2 with coughing most likely due to hyperventilation. The cyanosis observed could be due to peripheral circulatory effects of coughing.

Acute respiratory illness in children with acute lymphoblastic leukemia.

Ten of 70 children (14%) with acute lymphoblastic leukemia developed severe interstitial pneumonitis within three weeks after induction of central nervous system prophylactic therapy. The clinical picture was characterized by fever, cough, progressive dyspnea, and hypoxemia with complete resolution in one to three weeks, except in one patient who died during the acute illness from respiratory failure. P. carinii organisms were found in the lung tissue of only one patient. The etiology of the pneumonitis in the other nine children was probably viral, acquired or activated during a period of lymphopenia and immunosuppression. The morbidity and potential mortality from the pneumonitis warrants early recognition by open lung biopsy and intensive supportive therapy.