Morphometric evaluation of nitric oxide synthase isoforms and their cytokine regulators predict pulmonary dysfunction and survival in systemic sclerosis

Because histopathological changes in the lungs of patients with systemic sclerosis (SSc) are consistent with alveolar and vessel cell damage, we presume that this interaction can be characterized by analyzing the expression of proteins regulating nitric oxide (NO) and plasminogen activator inhibitor-1 (PAI-1) synthesis. To validate the importance of alveolar-vascular interactions and to explore the quantitative relationship between these factors and other clinical data, we studied these markers in 23 cases of SSc nonspecific interstitial pneumonia (SSc-NSIP). We used immunohistochemistry and morphometry to evaluate the amount of cells in alveolar septa and vessels staining for NO synthase (NOS) and PAI-1, and the outcomes of our study were cellular and fibrotic NSIP, pulmonary function tests, and survival time until death. General linear model analysis demonstrated that staining for septal inducible NOS (iNOS) related significantly to staining of septal cells for interleukin (IL)-4 and to septal IL-13. In univariate analysis, higher levels of septal and vascular cells staining for iNOS were associated with a smaller percentage of septal and vascular cells expressing fibroblast growth factor and myofibroblast proliferation, respectively. Multivariate Cox model analysis demonstrated that, after controlling for SSc-NSIP histological patterns, just three variables were significantly associated with survival time: septal iNOS (P=0.04), septal IL-13 (P=0.03), and septal basic fibroblast growth factor (bFGF; P=0.02). Augmented NOS, IL-13, and bFGF in SSc-NSIP histological patterns suggest a possible functional role for iNOS in SSc. In addition, the extent of iNOS, PAI-1, and IL-4 staining in alveolar septa and vessels provides a possible independent diagnostic measure for the degree of pulmonary dysfunction and fibrosis with an impact on the survival of patients with SSc.

Gas exchange at rest during simulated altitude in patients with chronica lung disease

Background. To characterize the gasometric and oximetric response to simulated altitudes of 3,100 m and sea level of patients with Chronic Obstructive Pulmonary Disease (COPD) and Interstitial Lung Disease (ILD) studied at 2,240 m above sea level. Methods. Consecutive stable patients with COPD and ILD were studied at the National Institute of Respiratory Diseases, a referral center for pulmonary diseases in Mexico City, and a healthy control group. The patients breathed room air (F1 O2 =0.21), for at least 15 min, then, a hypoxic mixture (F1 O2 =0.18, simulating 3,100 m), and finally, a hyperoxic mixture (F1 O2= 0.28, simulating sea level). Arterial blood gases and oxygen saturation were measured by a pulse oximeter at the end of each stage. Results. Twelve patients with COPD, 13 patients with ILD and 11 healthy controls were studied. The PaCO2 and pH were constant in the three study stages in both groups of patients and controls. A slope of PaO2 vs. altitude of 9 Torr per Km was found for each of the study's patients, either by simple linear regression or multiple regression, which is identical to that previously obtained at sea level with COPD patients (Gong et al.). Oxygen desaturation per Km of altitude change was alinear, higher for the hypoxic than for the hyperoxic challenge and more severe for the most hypoxic patients. Conclusions. Exposure test to simulated altitudes are safe, and orient the physician concerning the patient's condition at altitudes different from the place where the measurement is done. Alveolar ventilation remains constant despite hypoxia or hyperoxia during the challenges. A computer model of the lung reproduces many of the findings in the challenges of this study