Chronic Obstructive Pulmonary Disease as a Main Factor of Premature Aging.

(1) Background: Chronic obstructive pulmonary disease (COPD) is defined as an inflammatory disorder that presents an increasingly prevalent health problem. Accelerated aging has been examined as a pathologic mechanism of many chronic diseases like COPD. We examined whether COPD is combined with accelerated aging, studying two hormones, dehydroepiandrosterone (DHEA) and growth hormone (GH), known to be characteristic biological markers of aging. (2) Methods: Data were collected from 119 participants, 70 (58.8%) COPD patients and 49 (41.2%) from a health control group over the period of 2014⁻2016 in a spirometry program. Information about their medical history, tobacco use, and blood tests was obtained. (3) Results: The average age of the health control patients was 73.5 years (SD = 5.5), and that of the COPD patients was 75.4 years (SD = 6.9). Both groups were similar in age and sex. A greater proportion of smokers were found in the COPD group (87.1%) versus the control group (36.7%). The majority of COPD patients were classified as STAGE II (51.4%) and STAGE III (37.1%) according to GOLD (Global Initiative for Chronic Obstructive Pulmonary Disease). Levels of DHEA (SD = 17.1) and GH (SD = 0.37) were significantly lower in the COPD group (p < 0.001) compared to those in the controls (SD = 26.3, SD = 0.79). DHEA and GH were more significant and negatively correlated with age. The regression equation of DHEA with age produced a coefficient equal to 1.26. In this study, the difference in DHEA between COPD patients and controls was, on average, 30.2 µg/dL, indicating that the biological age of a COPD patient is on average about 24 years older than that of a control subject of the same age. Similarly, the difference in GH between COPD patients and controls was, on average, 0.42 ng/mL, indicating that the biological age of a COPD patient is on average about 13.1 years older than that of a control subject of the same age. (4) Conclusions: The findings of our study strongly suggest the presence of premature biological aging in COPD patients. Their biological age could actually vary from 13 to 23 years older than non-COPD controls according to DHEA and GH variation.

Role of histamine in altering fluid recycling in normal and post-traumatic rabbit peritoneum.

This study aims to investigate if histamine induces electrochemical alterations in the normal and post-traumatic peritoneum. Peritoneal rabbit specimens were obtained before surgery and 10 days post-operatively and were mounted in Ussing chambers. Histamine solutions were added facing the intra-peritoneal and outer-peritoneal surface. Dimetindene maleate-, cetirizine-, and ranitidine-pretreated specimens were used to investigate histamine receptor involvement, whereas amiloride- and ouabain-pretreated specimens were used to investigate ion transportation blockage involvement. Trans-mesothelial resistance (R(TM)) was determined. Histamine-increased R(TM) intra-peritoneally and decreased it outer-peritoneally. A less intense effect was induced in post-traumatic specimens. Dimetindene maleate, cetirizine, amiloride, and ouabain totally inhibited this effect, whereas ranitidine only had a partial effect. Histamine induces electrochemical alterations in the normal and post-operative peritoneum. This effect is mediated by interaction with histamine receptors, hindering the normal process of ion trans-mesothelial transportation.

IGF-1 alters the human parietal pleural electrochemical profile by inhibiting ion trans-cellular transportation after interaction with its receptor.

OBJECTIVE: The effect of IGF-1 in the human pleural permeability and the underlying mechanisms involved were investigated. DESIGN: Specimens from thoracic surgical patients were mounted in Ussing chambers. Solutions containing IGF-1 (1 nM-100 nM) and IGF-1 Receptor Inhibitor (1 µΜ), amiloride 10 µM (Na(+) channel blocker) and ouabain 1 mM (Na(+)-K(+) pump inhibitor) were used in order to investigate receptor and ion transporter involvement respectively. Trans-mesothelial Resistance (R(TM)) across the pleural membrane was determined as a permeability indicator. Immunohistochemistry for IGF-1 receptors was performed. RESULTS: IGF-1 increased R(TM) when added on the interstitial surface for all concentrations (p=.008, 1 nM-100 nM) and decreased it on the mesothelial surface for higher concentrations (p=.046, 100 nM). Amiloride and ouabain inhibited this effect. The IGF-1 Receptor Inhibitor also totally inhibited this effect. Immonuhistochemistry demonstrated the presence of IGF-1 receptors in the pleura. CONCLUSIONS: It is concluded that IGF-1 changes the electrophysiology of the human parietal pleura by hindering the normal ion transportation and therefore the pleural fluid recycling process. This event is achieved after IGF-1 interaction with its receptor which is present in the human pleura.

Two-year mortality of patients with COPD in primary health care: an observational study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) remains a significant cause of morbidity and mortality, with high rates of underdiagnosis. There are no studies about following up COPD patients in primary health care. The aim of the current study was to estimate two-year mortality for COPD patients in primary care and assess the parameters associated with mortality. METHODS: A total of 263 patients with a new COPD diagnosis were followed up for two years. Follow-up included phone contacts every six months for assessment of vital status, and re-examination visits every year after the initial diagnosis. Visits included performance on spirometry, assessment of smoking status, evaluation of adherence with treatment, and assessment of the number of exacerbations during the previous year. RESULTS: One hundred and eighteen patients with COPD completed the study. The overall mortality was 27.9%. Most patients had quit smoking two years after the initial diagnosis, whereas the percentage of patients showing high adherence with treatment was 68%. Parameters associated with two-year mortality were age and coronary heart disease comorbidity. CONCLUSION: The mortality of patients with COPD in primary care remains significantly high, whereas adherence with treatment remains significant low. Age, smoking status, and a history of depression are major determinants of mortality in primary health care.

Nonsteroidal anti-inflammatory drugs alter the human mesothelial pleural permeability via ion cellular transportation by inhibiting prostaglandin synthesis.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) are used in clinical practice as analgesics or anti-inflammatory drugs. Studies have implicated them in participating in permeability throughout various tissues such as the kidneys and lungs. OBJECTIVE: The effect of NSAIDs on the pleural permeability and the underlying mechanisms whereby this effect is mediated were investigated. METHODS: Parietal pleural specimens were obtained from patients subjected to thoracic surgery and were mounted in Ussing chambers. Solutions containing paracetamol, acetylsalicylic acid, diclofenac, lornoxicam, parecoxib and ibuprofen were added in the chambers facing the pleural and the outer-pleural surface. Prostaglandin E(2) was similarly used to investigate prostaglandin synthesis involvement at low and high doses. Amiloride- and ouabain-pretreated specimens were used in order to investigate ion transportation involvement. Transmesothelial resistance (R(TM)) was determined as a permeability indicator. RESULTS: Paracetamol, acetylsalicylic acid, diclofenac, lornoxicam and ibuprofen increased R(TM) on the pleural and outer-pleural surface, inhibited by amiloride and ouabain. Parecoxib had no effect on the R(TM). Prostaglandin decreased R(TM) on the pleural and outer-pleural surface inhibited by amiloride, ouabain and ibuprofen. CONCLUSION: NSAIDs, except parecoxib, induce a rapid decrease of the pleural permeability by inhibiting cellular transportation, an effect that is mediated by prostaglandin synthesis inhibition.

COPD prevalence and the differences between newly and previously diagnosed COPD patients in a spirometry program.

AIMS: To evaluate the prevalence and severity of COPD in a primary care population participating in a spirometry program. Differences between newly and previously diagnosed COPD patients were identified. METHODS: A spirometry program was conducted in 15 primary care centres. Visitors aged over 30 years who were willing to perform spirometry were included in this program. RESULTS: A total of 1,526 subjects provided acceptable spirometries. COPD prevalence in our population was 18.4%, of whom 69.0% were newly diagnosed. Most patients were classified as GOLD stages I and II (26.0% and 54.0%, respectively). COPD diagnosis was related to gender (men), age (older subjects), history of repeated respiratory infection in childhood, smoking (>10 pack-years) and presence of symptoms (cough, dyspnoea, wheezing). Variables related to newly diagnosed COPD were younger age and absence of chronic cough. CONCLUSIONS: A primary care spirometry program may identify a large proportion of undiagnosed COPD patients especially in the early stages of the disease. Newly diagnosed COPD patients were of younger age and presented with less symptoms. These results support the need for spirometry programs in primary care for early COPD detection.

Pleural electrophysiology alterations in spontaneous pneumothorax patients.

Physiology changes of the pleura in spontaneous pneumothorax (SP) patients are not known with its etiology remaining unclear. The aim of the study was to investigate the pleural electrophysiology profile of SP patients and to compare it with the normal pleural electrophysiology. Specimens from nine patients who underwent surgery for persistent SP were obtained after wedge resection (apical visceral) and apical pleurectomy (apical parietal) alongside with parietal specimens over the 8th-9th rib (caudal parietal). Specimens were mounted in Ussing chambers and trans-mesothelial resistance (R(TM)) was determined as a permeability indicator. Amiloride (Na(+) channel inhibitor) was used as an ion channel transportation inhibitor. R(TM) of apical visceral, apical parietal and caudal parietal pleura of SP patients was increased (P=0.042, 0.025 and 0.001, respectively) when compared to disease-free specimens obtained from lung lesion patients. Amiloride was unable to increase R(TM) in all cases. Histopathology of apical and caudal parietal specimens revealed inflammatory infiltration. In conclusion, pleural electrophysiology is altered in SP patients when compared with the electrophysiology of disease-free specimens. A similar observation was made for caudal pleura suggesting diffuse process that possibly involves inflammation as shown by the histopathology.

Pleural electrophysiology variations according to location in pleural cavity.

The aim of the study was to compare the electrophysiology profile of sheep pleura originated from different locations of the pleural cavity with the respective profile in humans. Sheep specimens obtained from upper and lower lung lobes, 1st-4th and 8th-12th rib, ventral-dorsal diaphragm and mediastinum were mounted between Ussing chambers. Human visceral tissues were obtained from patients subjected to lobectomy. Trans-mesothelial resistance (R(TM)) was determined as an indicator of the tissue permeability, while amiloride and ouabain were used as inhibitors of cellular transportation via ion transporters. Control values R(TM) were low in lower lobe visceral, caudal costal parietal and diaphragmatic pleura. Amiloride increased R(TM) at all locations except upper visceral and mediastinum. Higher R(TM) increases were found in caudal parietal and dorsal diaphragmatic samples. Ouabain increased R(TM) of lower visceral, caudal parietal and diaphragmatic pleura but not of mediastinal specimens. Observations made in sheep tissue were comparable with human visceral, parietal and mediastinal regions. In conclusion, results suggest heterogeneity of trans-mesothelial permeability among different pleural locations in sheep as was the case for humans. Thoracic surgeons should consider physiology function of each part of pleural cavity before pleural tissue manipulation. Observations made in sheep may be used to understand human physiology.

Human parietal pleura present electrophysiology variations according to location in pleural cavity.

The aim of the study was to investigate if human pleura from different anatomical locations presents electrophysiology differences. Specimens were stripped over the 2nd-5th rib (cranial), 8th-10th rib (caudal), and mediastinum during open surgery and were mounted between Ussing chambers. Amiloride and ouabain were added towards mesothelial surface and trans-mesothelial potential difference (PD) was measured after 1, 5, 10 and 20 min. Trans-membrane resistance (R) was calculated from Ohm's law. R increased after amiloride addition, for cranial (net increase of 0.40 Omega x cm(2)) and caudal (1.16 Omega x cm(2)) pleural pieces. Mediastinal pleura R remained unchanged (0.09 Omega x cm(2)). R increase was higher for caudal than cranial (P=0.029) or mediastinal tissues (P=0.002). R increased after ouabain addition for caudal (1.35 Omega x cm(2)) and cranial (0.56 Omega x cm(2)) pleural pieces. Mediastinal pleural tissue did not respond (0.20 Omega x cm(2)). Caudally located pleura responded greater than cranial (P=0.043) or mediastinal (P=0.003) pleural tissues. Human pleura shows electrophysiology differences according to the location within the pleural cavity. Surgeons may waste mediastinal pleura when needed but should leave intact caudal parietal pleura, which seems to be electrophysiologically the most important part of the pleural cavity.