Traian Mihaescu

Fatigue and serum testosterone in obstructive sleep apnea patients

Obstructive sleep apnea (OSA)‐related fatigue is a common understudied symptom. Fatigue is associated with low serum testosterone level in non‐OSA patients. No data are available about this association in OSA patients.

Serum trace metal and ceruloplasmin variability in individuals treated for pulmonary tuberculosis.

SETTING Investigation of trace metal behaviour during the treatment of active pulmonary tuberculosis (PTB) patients residing in Romania. OBJECTIVE To assess, follow and identify serum iron (Fe), copper (Cu) and zinc (Zn) levels in patients diagnosed and treated for active PTB. DESIGN Chemical and statistical analysis of various biochemical parameters in 47 subjects diagnosed with active PTB and 170 healthy Romanian residents. RESULTS Copper and ceruloplasmin levels were increased in patients with active PTB compared to the control group (P < 0.01), while the serum Zn level was significantly lower than in healthy subjects (P < 0.01) or within the normal range. The present study shows that there is a significant correlation between serum Cu concentrations and ceruloplasmin. CONCLUSIONS This study provides preliminary evidence that Zn and Fe redistribution is operating as a primary host defence mechanism to reduce the availability of metals for microbial metabolism during infection. The study also calls attention to the fact that anti-tuberculosis treatment is sufficient to enhance the concentration of the antioxidant species (Cu and ceruloplasmin). The data obtained suggest that serum Cu, Zn and Cu/Zn levels may serve as indirect pointers in the diagnosis of a disease but they cannot be considered as specific markers for TB.

Serum testosterone and depressive symptoms in severe OSA patients

Obstructive sleep apnoea (OSA), also characterised by hypoxia‐related sleep‐ fragmentation, has been studied in relation to depression and serum testosterone deficit. In middle‐aged men, it has been reported the association between depressive mood and low serum testosterone level; however, no data are available about this association in OSA patients. Therefore, the aim of this study was to investigate in adult obese males, affected by severe OSA, the relationship between serum testosterone concentration and depressive symptoms, in order to identify among all measured parameters (serum testosterone morning concentration, polysomnography parameters, body mass index, Epworth Sleepiness Scale) those predictors for OSA‐related depression. Forty patients diagnosed with severe OSA and forty subjects for the control‐matched group were enroled in the study. The results indicated that the serum testosterone in OSA group was significantly lower than in controls. In addition, the OSA group presented a level of depression although moderate, yet significantly higher than controls. Furthermore, a statistically significant inverse correlation has been found between serum testosterone level and depressive symptoms. Among all variables, serum testosterone level was shown to be the only independent variable significantly predictor for depression in OSA patients.

Restoring the Salivary Cortisol Awakening Response Through Nasal Continuous Positive Airway Pressure Therapy in Obstructive Sleep Apnea

Partial and largely conflicting data are currently available on the interplay between obstructive sleep apnea (OSA) and hypothalamus-pituitary-adrenal axis (HPA) activity in adult obese men. This study was performed to evaluate the daily trajectories of salivary cortisol, specifically with respect to the salivary cortisol awakening response (CAR), a common method used to assess HPA axis activity. The main findings of this study were that adult male obese subjects who were newly diagnosed with severe OSA showed the following: (1) a flattening of the CAR; (2) levels of cortisol at awakening that were lower than those of the controls; and (3) maintenance of the physiological circadian activity of the HPA axis, with the highest hormone concentrations produced in the morning and the lowest in the evening. This study was also designed to investigate the effects of 3 and 6 mos of treatment with continuous airways positive pressure (CPAP). CPAP use resulted in a significant recovery of the sleep patterns disrupted by OSA; moreover, mild neuropsychological signs of depression and anxiety in severe OSA patients were concomitantly progressively improved by CPAP treatment. Furthermore, this study reports that 3 and 6 mos of CPAP therapy restored the presence of CAR and was able to significantly reduce the difference in the morning cortisol levels between the OSA and control groups. In conclusion, we report here that compared with obese nonapneic matched controls, OSA patients present a dysregulation of HPA axis activity, as shown by the flattening of the diurnal pattern of cortisol production in response to repeated challenge due to hypoxia and sleep fragmentation. This dysregulation was especially detectable in the first hour after awakening and restored after 3 and 6 mos of treatment with CPAP.

Pharmacotherapy of cough-variant asthma.

Cough-variant asthma is considered as an asthma subset in which chronic cough is the only symptom. It is believed to be more frequent and, hence, sometimes overdiagnosed in children, and shares with typical asthma eosinophilic airway inflammation and consequent bronchial hyper-responsiveness. Presently available therapies consist of bronchodilators, inhaled or oral corticosteroids, or leukotriene modifiers. However, the long-term efficacy of these agents in adults and children is not known. This review focuses on current therapies used for cough variant asthma, also highlighting potential therapeutic targets for this condition.

Inhaled therapy for stable chronic obstructive pulmonary disease

Bronchodilators (anticholinergic drugs and β2-agonist drugs) represent the mainstay of chronic obstructive pulmonary disease treatment and can be combined with inhaled corticosteroids for greater efficacy. This review examines the role of short- and long-acting cholinergic drugs, together with that of short- and long-acting β2-agonist drugs. A brief analysis of the long-term use of corticosteroids in chronic obstructive pulmonary disease is made, with a review of the safety and possible side effects. Combination therapy is more frequently used due to its practicality and capacity to enhance compliance. The main studies on treatment combinations are also analyzed in this paper.

Imbalance in the diurnal salivary testosterone/cortisol ratio in men with severe obstructive sleep apnea: an observational study

INTRODUCTION The complex relationship between sleep disorders and hormones could lead to alterations in the production of cortisol and testosterone in obstructive sleep apnea (OSA) patients. OBJECTIVE The purpose of this study was to determine the diurnal trajectories of salivary free-testosterone, free-cortisol and their ratio (T/C). METHODS Ten subjects newly diagnosed with OSA, based on nocturnal polysomnography evaluation and excessive daytime sleepiness, and seven matched controls were consecutively recruited. Cortisol and testosterone were measured in salivary samples collected upon awakening, at noon and in the evening. The psychometric evaluation of anxiety/depression and referred sexual function disturbances was performed to evaluate the presence of neuropsychological comorbidities. RESULTS AND CONCLUSION The main finding was that OSA subjects displayed hypocortisolism upon awakening and a significant reduction in testosterone concentration in the evening in comparison with the control group, which has maintained the physiological testosterone and cortisol diurnal fluctuation, with higher hormone concentrations in the morning and lower concentrations in the evening. The use of data from multiple diurnal measurements rather than a single point allowed the detection of T/C ratio changes of opposite signs at the beginning and end of the day: the OSA subjects had a higher T/C ratio than the controls in the morning, while their T/C ratio was significantly lower than that of the controls in the evening. The imbalances in the anabolic-catabolic diurnal equilibrium suggest that OSA is associated with a dysregulation of the hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes, potentially an underlying cause of some of the neuropsychological comorbidities observed in OSA patients.

Hospitalizations and mortality in the Lung Health Study

The Lung Health Study previously reported that an aggressive smoking cessation intervention significantly reduced the decline of the forced expiratory volume in 1 sec in middle-aged patients without clinical symptoms, but with mild airway obstruction. This effect was the most evident during the first year after quitting smoking and moreover, persisted over the study period (5 years). In the current report, the impact of smoking cessation on mortality and morbidity was assessed in the same population. Being male, age, higher blood diastolic blood pressure were the main mortality risk-factors, whereas being female and alcohol consumption were risk-factors for subsequent respiratory disease.

Analysis of possible diagnostic errors - a proposed formula to improve the management of respiratory patients

The diagnostic errors are a controversial but real-life topic considered a leading cause of death and unintended harm due to medical-care procedures. We proposed a formula to assess the possibility to identify the diagnostic errors using a database analysis of patients admitted and released from the Clinic of Pulmonary Diseases. We built a database from the admittances and releases during a 21 months period and use a trigger based on a score. Our analysis found out that 48% of patients released had a different diagnostic on release than on admittance. 11,8% patients were re-admitted after less than 30 days upon their release and 871 Patients (6,1% from total, 51,3% from re-admittances) were readmitted with a different diagnosis. This way, we found 8% of our database entries can be assessed as diagnostic errors, the percent being aligned to international findings.