Quality of life among pulmonary hypertension patients in Finland.

BACKGROUND: The purpose of the study was to examine pulmonary hypertension (PH) patients' quality of life (QOL) for the first time in Finland. METHODS: This was a non-interventional, cross-sectional study. The SF-36v2 questionnaire was sent to the PH patients who had been referred to or followed up on at the Helsinki University Central Hospital's pulmonary clinic for idiopathic pulmonary arterial hypertension, associated pulmonary arterial hypertension (APAH), or chronic thromboembolic PH (CTEPH). The patients were on pulmonary arterial hypertension (PAH) - specific drugs, were at least 18 years old, and had signed an informed consent. RESULTS: There were 62 patients who fulfilled the inclusion criteria, and 53% of respondents rated their health as moderate. Similarly, 55% of respondents rated their health status approximately the same compared to their situation 1 year ago. QOL was impaired in all other subscales, except for the mental health and mental component score. A majority of patients suffered from PH symptoms, which worsened their QOL. The greatest impact on their QOL was associated with a high World Health Organization (WHO) functional class (FC), poor performance in a 6-min walking test (6MWT), symptoms, oxygen therapy, elevated pro-brain natriuretic peptide, pericardial effusion, APAH etiology, and being retired from work. CONCLUSIONS: The respondents had a reduced QOL, compared to the general population, in all other subscales, except for mental health. APAH patients had the worst QOL. Good results in functional capacity measures (WHO FC, 6MWT) were associated with a better QOL. Patients' QOL can be improved by reducing the symptoms of PAH.

Nitric oxide synthases are associated with bronchial dysplasia.

Recent studies suggest that reactive oxygen (ROS) and nitrogen species (RNS) are highly associated with the pathogenesis of cigarette smoke related lung diseases but their role in the malignant conversion of bronchial epithelium is unclear. The immunohistochemical expression of inducible, endothelial and neuronal nitric oxide synthases (iNOS, eNOS and nNOS) and nitrotyrosine as a biomarker of oxidative/nitrosative stress was evaluated in 79 cases including 13 non-smokers, 20 smokers without chronic obstructive pulmonary disease (COPD), 22 with COPD and 24 with metaplasia-dysplasia-sequence of the bronchial epithelium. Normal lung of non-smokers was mainly negative for nitrotyrosine, while it was higher in the alveolar macrophages of cigarette smokers and COPD than in non-smokers (p=0.025, p<0.001), and in the alveolar epithelium of smokers and COPD than in non-smokers (p=0.049). There were no major differences in the nitrotyrosine immunoreactivity between the metaplastic/dysplastic lesions and bronchial epithelium of cigarette smokers. Inducible NOS and nNOS were mainly non-detectable or weak in the normal looking bronchial epithelium of smokers and COPD, whereas metaplasia and dysplasia showed positivity for iNOS (22/24) and nNOS (14/24) in the majority of cases. Strong immunoreactivity for iNOS and nNOS was also found more often in dysplastic than metaplastic (p=0.011 and p=0.049, respectively) specimens. Thus, smoking can cause protein nitration also in normal lung. Prominent iNOS and nNOS immunoreactivity in the metaplasia-dysplasia-lesions suggests a divergent role of NOSs in lung carcinogenesis.

High expression of nitric oxide synthases is a favorable prognostic sign in non-small cell lung carcinoma.

Immunohistochemical expression of neuronal (n), endothelial (e), and inducible (i) NOS and their association with the type, grade, apoptotic index, proliferation of tumors and the survival of patients were investigated in 89 biopsies of non-small cell lung carcinoma (NSCLC). In tumor cells, expression of iNOS was detected in 35/89 (40%) cases, while 79/89 (89%) and 72/89 (81%) cases showed weak to intense positivity for eNOS and nNOS, respectively. Strong eNOS staining was seen significantly more often in adenocarcinomas than in squamous cells carcinomas (p=0.016), and iNOS immunoreactivity was seen more often in grade I-II tumors than in grade III tumors (p=0.024). There was no significant difference between the low and high apoptotic indexes or between the low and high proliferation rates of tumors in any instance of NOS staining. The patients with tumors showing high nNOS expression tended to have better survival than the others (p=0.06, log-rank; p=0.04, Bresow; p=0.048, Tarone-Ware). Similarly, the patients with tumors showing high expression of iNOS, eNOS and nNOS, as determined by a combined sum index, had a better survival than those with a low sum index for these enzymes (p<0.05). The results show intense expression of eNOS and nNOS, and moderate expression of iNOS in tumor cells of non-small cell carcinoma. Intense NOSs expression seems to be a favorable prognostic sign in non-small cell lung carcinoma.

Modulation of DNA single-strand breaks by intracellular glutathione in human lung cells exposed to asbestos fibers.

We investigated the role of glutathione and nitric oxide synthase (NOS) in fiber-induced cell and DNA toxicity using alkaline (pH 13) single-cell gel electrophoresis (the Comet assay). Transformed cultured human pleural mesothelial (MeT-5A) cells and alveolar epithelial cells (A549) were exposed to crocidolite asbestos fibers (1-10 microg/cm(2)) in the presence of buthionine sulfoximine (BSO) or L-arginine-methyl ester (L-NAME). BSO inhibits gamma-glutamylcysteine synthetase (gamma-GCS) and causes glutathione depletion, and L-NAME inhibits nitric oxide generation. Studies were also conducted to assess the expression of the heavy and light subunits of gamma-GCS in human pleural mesothelium and bronchial epithelium in vivo and the induction of inducible NOS (iNOS) by asbestos fibers. Asbestos fibers caused DNA single-strand breaks, and the process was significantly enhanced by BSO (69% compared to the non-treated cells). A549 cells had a 3.5-fold glutathione content compared to MeT-5A cells, which was consistent with the higher resistance of these cells against oxidants and fibers. Flow cytometry of iNOS showed no change of iNOS by the fibers in either cell type in vitro. L-NAME had no effects on the DNA single-strand breaks in the Comet assay, either. Studies on lung biopsies showed that the immunoreactivities of both gamma-GCS subunits were very low in healthy human mesothelium in vivo. We conclude that glutathione may play an essential role in protecting intact cells against fiber-induced oxidative DNA alterations, and low gamma-GCS reactivity in pleural mesothelium may be associated with the high sensitivity of mesothelial cells to fiber-induced toxicity.