Manos Alchanatis

Daytime Pulmonary Hypertension in Patients with Obstructive Sleep Apnea

Background: Limited information exists regarding the development of pulmonary hypertension in patients with obstructive sleep apnea (OSA) in the absence of lung and heart comorbidity. Objectives: The aims of this study were to investigate whether OSA patients without any other cardiac or lung disease develop pulmonary hypertension, and to assess the effect of continuous positive airway pressure (CPAP) treatment on pulmonary artery pressure (PPA). Methods: Twenty-nine patients aged 51 ± 10 years with OSA and 12 control subjects were studied with pulsed-wave Doppler echocardiography for estimation of PPA before and after 6-month effective treatment with CPAP. Results: A significantly higher mean PPA was found in OSA patients as compared to control subjects (17.2 ± 5.2 vs. 12.1 ± 1.9 mm Hg, p < 0.001). Six out of the 29 OSA patients had mild pulmonary hypertension (PPA ≧ 20 mm Hg). Significant differences were observed between pulmonary hypertensive and normotensive OSA patients with respect to age (62 ± 4 vs. 48 ± 15 years, respectively, p < 0.05), body mass index (41 ± 7 vs. 32 ± 4 kg/m2, p < 0.02) and daytime PaO2 (81 ± 9 vs. 92 ± 9 mm Hg, p < 0.05). CPAP treatment was effective in reducing mean PPA in both groups of pulmonary hypertensive and normotensive OSA patients (decreases in PPA from 25.6 ± 4.0 to 19.5 ± 1.5 mm Hg, p < 0.001; from 14.9 ± 2.2 to 11.5 ± 2.0 mm Hg, respectively, p < 0.001). Conclusions: A proportion (20.7%) of OSA patients without any other lung or heart disease and characterized by older age, greater obesity and lower daytime oxygenation develop mild pulmonary hypertension which has been partially or completely reversed after 6-month CPAP treatment. In conclusion, OSA alone constitutes an independent risk factor for the development of pulmonary hypertension.

Evidence for left ventricular dysfunction in patients with obstructive sleep apnoea syndrome

There is limited information on the development of left ventricular (LV) dysfunction in patients with obstructive sleep apnoea (OSA) in the absence of lung and cardiac comorbidity. This study aimed to investigate whether OSA patients without heart morbidity develop LV dysfunction, and to assess the effect of continuous positive airway pressure (CPAP) on LV function. Twenty-nine OSA patients and 12 control subjects were studied using technetium-99m ventriculography to estimate LV ejection fraction (LVEF), LV peak emptying rate (LVPER), time to peak emptying rate (TPER), peak filling rate (LVPFR) and time to peak filling rate (TPFR) before and after 6 months of treatment with CPAP. A significantly lower LVEF was found in OSA patients, compared to control subjects, (53±7 versus 61±6%) along with a reduced LVPER (2.82±0.58 versus 3.82±0.77 end-diastolic volumes·s−1). Furthermore, OSA patients had significantly lower LVPFR (2.67±0.71 versus 3.93±0.58 end-diastolic volumes·s−1) and delayed TPFR (0.19±0.04 versus 0.15±0.03 s) in comparison with the control group. Six-months of CPAP treatment was effective in significantly improving LVEF, LVPER, LVPFR and TPFR. In conclusion, obstructive sleep apnoea patients without any cardiovascular disease seem to develop left ventricular systolic and diastolic dysfunction, which may be reversed, either partially or completely, after 6 months of continuous positive airway pressure treatment.

Sleep apnea-related cognitive deficits and intelligence: an implication of cognitive reserve theory

Cognitive deficits in patients with obstructive sleep apnea syndrome (OSAS) are well demonstrated, but the pathophysiology of these deficits is still controversial, as the relationship between OSA severity and cognitive deficits is usually weak. Our study considers the possible relationship between OSA‐related cognitive deficits and the overall intellectual function of OSA patients. Forty‐seven OSA patients and 36 normal individuals underwent a neuropsychological battery test assessing attention and alertness. According to the resulting IQ score, patients and controls were divided into a high‐intelligence group (IQ ≥ 90th percentile) and a normal‐intelligence group (50 ≤ IQ < 90%ile). Between the two patient groups there were no significant differences noticed, regarding OSA severity or sleepiness. High‐intelligence patients showed the same attention/alertness performance compared with the high‐intelligence controls. On the contrary, patients with normal‐intelligence showed attention/alertness decline compared with the normal‐intelligence control group. The two patient groups were re‐examined with the same battery test after at least 1 year of CPAP treatment. At re‐examination neither patient group showed any differences regarding attention and alertness compared with the control groups. We assume that high‐intelligence may have a protective effect against OSA‐related cognitive decline, perhaps due to increased cognitive reserve.

Left Ventricular Function in Patients with Obstructive Sleep Apnoea Syndrome before and after Treatment with Nasal Continuous Positive Airway Pressure

Background: Previous studies have yielded disparate results regarding the effect of obstructive sleep apnoea (OSA) syndrome on left ventricular (LV) function. Objectives: In order to clarify this, we performed a prospective study investigating OSA patients with no history of systemic hypertension, coronary artery disease, myocardial, pericardial or valvular problems, asthma or chronic obstructive pulmonary disease before and after treatment with nasal continuous positive airway pressure (nCPAP). Methods: Fifteen patients (3 women, 12 men) with an apnoea/hypopnoea index >15 (mean ± SD = 52 ± 21) were studied with complete polysomnography, ambulatory blood pressure monitoring, M-mode two-dimensional echocardiography and pulsed Doppler echocardiography in two phases, i.e. before and after 12–14 weeks of nCPAP therapy. We measured systolic and diastolic blood pressure (BP) separately in the daytime and night-time, isovolumic relaxation time (IVRT), the ratio of peak early filling velocity (E) to peak late velocity (A) diastolic transmitral flow (E/A), posterior wall thickness (PWT) and septal thickness (IVST). The shortening fraction (SF) was also calculated. Eleven overweight non-apnoeic normal subjects matched for age were used as the control group. Results: Our results showed that the patient group exhibited, before treatment, LV diastolic, but not systolic, dysfunction compared with the normal group (IVRT = 94.3 ± 11.6 ms, p < 0.05; E/A = 0.94 ± 0.26, p < 0.02; SF = 39.9 ± 4.1%, not significant (NS); IVST = 9.9 ± 1.2 mm, NS; PWT = 8.3 ± 1.2 mm, NS). Moreover, the patient group developed diastolic hypertension both in the daytime and night-time (BP/diastolic/daytime = 93.3 ± 9.2 mm Hg, BP/diastolic/night-time = 90.3 ± 10.7 mm Hg). After 12–14 weeks of nCPAP treatment (no change in body mass index), significant improvement in LV diastolic function and a drop in blood pressure were noticed (IVRT = 85.6 ± 8.8 ms, p < 0.05; E/A = 1.07 ± 0.3, p < 0.05; BP/diastolic/daytime = 86.3 ± 5.5 mm Hg, p < 0.02; BP/diastolic/night-time = 83.9 ± 8.6 mm Hg, p < 0.05) in our patient group. Conclusions: We conclude that repetitive apnoeas/hypopnoeas are very important factors in the development of both LV diastolic dysfunction and diastolic systemic hypertension in patients with OSA syndrome. Treatment with nCPAP leads to significant improvement in both ventricular function and systemic hypertension.

The incremental effect of obstructive sleep apnoea syndrome on arterial stiffness in newly diagnosed essential hypertensive subjects.

Objective Although obstructive sleep apnoea syndrome (OSAS) is accompanied by an increased atherosclerotic cardiovascular disease burden, its relationship with arterial stiffness is not yet well determined. We investigated whether essential hypertensive individuals with OSAS are characterized by increased arterial stiffness. Methods Our study population consisted of 46 consecutive patients with newly diagnosed untreated stage I–II essential hypertension suffering from OSAS (35 men, aged 49 ± 8 years) and 53 hypertensive individuals without OSAS, matched for age, sex, and smoking status. All subjects underwent polysomnography, echocardiography and aortic stiffness evaluation by means of carotid–femoral pulse wave velocity (c–fPWV) measurements. Results Hypertensive subjects with OSAS [apnoea/hypopnoea index (AHI) ≥ 5] compared with hypertensive subjects without OSAS (AHI < 5) demonstrated increased levels of body mass index (31.4 ± 4 versus 29.3 ± 4 kg/m2, P = 0.015), office systolic/diastolic blood pressure (151/99 versus 145/94 mmHg, respectively, P < 0.05, for both cases) and relative wall thickness (RWT; 0.46 ± 0.06 versus 0.42 ± 0.07, P = 0.010). Hypertensive subjects with OSAS compared with those without OSAS had significantly increased c–fPWV by 9% (8.56 ± 0.49 versus 7.85 ± 0.93 m/s, P = 0.001) and this difference remained significant even after adjustment for confounders (P = 0.04). In the total study population, c–fPWV was correlated with age (r = 0.35, P = 0.015), office systolic blood pressure (r = 0.30, P = 0.007), RWT (r = 0.30, P = 0.03), logAHI (r = 0.389, P = 0.0001) and minimum oxygen saturation (r = −0.418, P = 0.0001). Conclusions OSAS has a significant incremental effect on aortic stiffening in the setting of middle-aged essential hypertensive subjects. This finding suggests that the presence of OSAS in a hypertensive patient accelerates vascular damage, increasing cardiovascular risk.

Effects of continuous positive airway pressure on blood pressure in hypertensive patients with obstructive sleep apnea: a 3-year follow-up.

Objective: Several studies have reported a small yet significant decrease in blood pressure (BP) with continuous positive airway pressure (CPAP) application in patients with obstructive sleep apnea (OSA). We investigated the long-term efficiency of CPAP in the management of hypertensive patients with OSA on top of conventional antihypertensive medication. Methods: We followed 91 nonsleepy patients (aged 54 ± 9 years, 69 men) with essential hypertension and newly diagnosed moderate-to-severe OSA (apnea–hypopnea index, 38 ± 24 events/h on polysomnography) for a mean period of 3.1 years, after switching them to antihypertensive treatment targeting office BP less than 140/90 mmHg (<130/80 mmHg in diabetic patients). Participants were defined as on-CPAP if they adhered to CPAP treatment during the whole follow-up period (N = 41), whereas those that did not follow CPAP therapy served as controls (N = 50). Results: By the end of follow-up, on-CPAP patients and controls exhibited similar SBP and DBP levels (133 ± 12 versus 133 ± 13 mmHg, 84 ± 9 versus 85 ± 9 mmHg, respectively, P > 0.05 for all), number of patients with controlled hypertension (71 versus 70%, P > 0.05), and number of antihypertensive drugs needed to achieve BP control (2.28 ± 1.09 versus 2.11 ± 0.72, P > 0.05). In a subgroup of patients (N = 34) in whom ambulatory BP monitoring was also performed, 24-h BP levels did not differ between the two groups (125 ± 10/76 ± 7 mmHg versus 123 ± 11/75 ± 10 mmHg, P > 0.05). In multiple regression models, CPAP application was not associated with changes in BP levels. Conclusion: In nonsleepy, hypertensive, OSA patients on conventional antihypertensive treatment, long-term CPAP application is not associated with lower BP levels or a need for less antihypertensive drugs for BP control.

Prophylactic cranial irradiation in non-small cell lung cancer patients: who might be the candidates?

Objectives Brain metastases (BMs) often advance the course of non-small cell lung cancer (NSCLC). We performed an observational study in order to investigate the possible correlation of selected clinical and epidemiological factors with BM appearance in patients suffering from different histological subtypes of NSCLC stage I–IV. Methods The study included 161 consecutive patients with NSCLC. Analyzed data included patient- and tumor-related characteristics. Results Thirty-nine patients (24.2%) presented BMs within 12 (0–36) weeks of diagnosis. BMs decreased the mean overall survival significantly (15.6 versus 50.7 weeks, P < 0.001), with hazard ratio (95% confidence interval) 3.60 (2.42–5.35). The age of the patients with BM was significantly lower than that of the patients without BM (60.8 ± 8.9 versus 66.5 ± 8.5, P < 0.001). Patients with BM had significantly higher pack-years consumption (75.9 ± 23.9 versus 58.9 ± 31.9, P = 0.003) and larger tumor size compared with patients without BM (size in mm: 55.1 ± 20.1 versus 45.9 ± 19.3, P = 0.012). The presence of BM was also correlated with the absence of lung (P < 0.001), bone (P = 0.005), and adrenal (P = 0.046) metastases. Conclusion Younger NSCLC patients with high tobacco consumption, large tumor size, and absence of metastases in other organs (lung, bones, adrenal metastases) are at high risk of BM appearance during the course of NSCLC and are candidates for prophylactic cranial irradiation early in the course of the disease.

Eosinophilic infiltration in the nasal mucosa of rhinitis patients: is it affected by the presence of asthma or the allergic status of the patients?

BACKGROUND Asthma and rhinitis often coexist, and there is evidence to suggest that they have similar histopathologic features. OBJECTIVE To examine whether the inflammatory infiltration in the nasal mucosa in rhinitis is affected by the presence of asthma and allergy. METHODS Nasal mucosa biopsy samples were collected from 44 individuals: 18 with rhinitis and asthma (9 allergic and 9 nonallergic), 16 with rhinitis and no asthma (8 allergic and 8 nonallergic), and 10 nonallergic control subjects. The alkaline phosphatase-anti-alkaline phosphatase method was applied to 6-microm-thick cryostat sections using monoclonal antibodies against T cells (CD4 and CD8) and eosinophils (EG2). Slides were counted blindly, and results are expressed as cells per high-power field. RESULTS Eosinophil counts were higher in the nasal mucosa of rhinitic patients vs controls. No differences in cellular infiltration were detected between rhinitic patients with and without asthma or between allergic and nonallergic patients. A trend toward higher CD4+ T-cell counts in the nasal mucosa of rhinitic patients was observed, whereas no differences were noted in CD8+ T-cell infiltration among the groups. CONCLUSION Inflammatory infiltration, characterized by the presence of eosinophils and CD4+ T cells, was similar in the nasal mucosa in noninfectious rhinitis irrespective of the presence of asthma or the allergic status of the patient.

Latest Therapeutic Novelties and Patents in Pulmonary Hypertension

Recent advances in technology and novel pharmaceutical research findings have added new grounds in the fields of medical treatment and quality of life of patients diagnosed with pulmonary arterial hypertension (PAH). Collective assessment of new data is mandatory and useful for specialist medical doctors. This review aims to present the latest therapeutic developments of the last two years (2009-2010) in PAH. Moreover, recent patents (of the year 2010) regarding therapeutic novelties in PAH that expand treatment modalities, are hereby presented.

Changes in BODE Quartiles After Pulmonary Rehabilitation Do Not Predict 2-Year Survival in Patients With COPD.

PURPOSE: Pulmonary rehabilitation (PR) has well documented positive effects in patients with chronic obstructive pulmonary disease (COPD). The BODE (body mass index, airflow obstruction, dyspnea, and exercise) index reflects the multicomponent nature of COPD. We aimed to determine whether changes in BODE quartiles after a PR program might affect 2-year survival and which characteristics drive changes in BODE quartiles after PR intervention. METHODS: Ninety-five patients with COPD participated in a PR program. The BODE index and anxiety, depression, and quality of life questionnaires were completed before and after the PR program. Five-year survival was recorded for all patients, irrespective of changes in BODE quartiles. RESULTS: Up to 62% of patients with COPD had an improvement in the BODE index, whereas 42% of patients had a change in BODE quartile. Survival did not differ between patients who did not and who did show an improvement in BODE quartiles, despite a trend in favor of the latter (log-rank P = .202). Similar results were observed for patients who did and did not demonstrate a change in the BODE index ≥2 (log-rank P = .679). Significant changes in BODE quartiles were mainly attributed to the duration of the disease, current smoking status, hospitalization rate in the previous year, and the presence of poorer quality of life, as well as to anxiety and depression at baseline. CONCLUSIONS: Pulmonary rehabilitation significantly influenced the BODE index. The significant changes in BODE quartiles were associated with the duration of the disease, current smoking status, increased hospitalization rate, poorer quality of life, anxiety, and depression at baseline, but failed to predict 2-year survival.