Daytime PaO2 in OSAS, COPD and the combination of the two (overlap syndrome).

BACKGROUND: OSAS and COPD are often associated with day-time hypoxemia. Overlap Syndrome (OS), the association between both diseases, increases the risk of day-time hypoxemia. The aim of this study was to investigate the mechanisms which could justify the low oxygen level and the effect of CPAP. METHODS: We performed a retrospective analysis in all patients referred to our institutes for suspected OSAS and who also underwent spirometry and blood gas analysis during our evaluation. Thus, 720 patients were selected. According to pulmonary function test parameters they were divided into 3 groups: OSAS (N = 466,65%); OS (N = 168,23%) and COPD (N = 86,12%). In order to evaluate the differences between the three groups, ANOVA analyses were carried out, whereas a multivariate analysis was performed in order to evaluate which factors determine the diurnal PaO(2). In 90 patients we also have the data on blood gas analysis after one year of CPAP treatment, so we evaluate the PaO(2) improvement in accordance with compliance to treatment in these patient subgroups. RESULTS: The OS group showed a lower level of daytime PaO(2) compared with OSAS patients and T90 was higher in OS compared with OSAS. A multivariate analysis showed that in the OS diurnal PaO(2) correlated with age (ß = -0.20) and moreover with FEV(1) (ß = 0.31) and T90 (ß = 0.37), while in the OSAS a correlation was found with FEV(1) (ß = -0.11) and mostly with BMI (ß = 0.25), age and T90. In all patients with good compliance to CPAP day-time PaO(2) improved. CONCLUSIONS: Our data suggest that day-time hypoxemia in OSA patients is largely determined by the increase of body weight and severity of nocturnal hypoxia. However, CPAP therapy has been shown to improve daytime PaO(2) values both in OSAS and in OS.

Effect of CPAP-therapy on bronchial and nasal inflammation in patients affected by obstructive sleep apnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) has been shown to be associated to upper and lower airways inflammation. Continuous positive airway pressure (CPAP) is the elective treatment of OSAS. The aim of the present study was to assess the effect of CPAP-therapy on airway and nasal inflammation. METHODS: In 13 non-smoking subjects affected by untreated OSAS and in 11 non-smoking normal volunteers, airway inflammation was detected by analyses of the induced sputum. In the OSAS group measurements were repeated after 1, 10 and 60 days of the appropriate CPAP treatment. In addition, in 12 subjects of the OSAS group, nasal inflammation was detected by the analysis of induced nasal secretions at baseline, and after 1, 10 and 60 days of CPAP treatment. RESULTS: OSAS patients, compared to normal controls, showed at baseline a higher percentage of neutrophils and a lower percentage of macrophages in the induced sputum. One, 10 and 60 days of appropriate CPAP-therapy did not change the cellular profile of the induced sputum. In addition, in the OSAS patients, the high neutrophilic nasal inflammation present under baseline conditions was not significantly modified by CPAP-therapy. Finally, no patients developed airway hyper-responsiveness after CPAP therapy. CONCLUSIONS: In OSAS subjects, the appropriate CPAP-therapy, while correcting the oxygen desaturation, does not modify the bronchial and nasal inflammatory profile.

Exhaled NO and iNOS expression in sputum cells of healthy, obese and OSA subjects.

BACKGROUND: Obstructive sleep apnoea (OSA) is associated with airways inflammation; a key role in this regard seems to be played by nitric oxide (NO). The aim of this study was to measure exhaled NO and expression of its enzyme, the inducible nitric oxide synthase (iNOS) in cells of induced sputum in OSA patients and in obese subjects without sleep apnoea and to correlate these inflammatory markers with severity of OSA. METHODS: We enrolled 18 obese patients with OSA (10 men, age 48.2 +/- 8.4 years), 15 obese patients without OSA (eight men, age 52.8 +/- 11 years) and 10 healthy subjects (five men, age 42 +/- 4 years). Exhaled NO was measured using a chemiluminescence analyser; iNOS expression was measured in the sputum cells by immunocytochemistry. RESULTS: Exhaled NO resulted significantly increased in OSA and in obese patients (23.1 +/- 2.1 and 17.9 +/- 2.1 p.p.b.) than in healthy subjects (7.2 +/- 0.6 p.p.b.; P < 0.001). OSA and obese patients showed a higher percentage of neutrophils and a lower percentage of macrophages in the induced sputum compared to healthy subjects. In addition, OSA and obese patients showed higher iNOS expression in neutrophils and in macrophages with respect to healthy subjects. A positive correlation between exhaled NO, iNOS expression and AHI was observed. CONCLUSIONS: These data confirm the presence of airway inflammation in OSA and in obese patients, and suggest the possible role for NO and iNOS expression in neutrophils of the induced sputum as noninvasive markers to identify and monitor the airway inflammation in these subjects.

Airway inflammation in patients affected by obstructive sleep apnea.

Obstructive sleep apnea (OSA) is characterised by repetitive episodes of upper airway occlusion during sleep. OSA has been shown to be associated with a variable degree of nasal inflammation, uvula mucosal congestion and airway hyperreactivity. The upper airway inflammation, whose clinical importance is uncertain, is characterised by leukocytes infiltration and interstitial oedema. In addition, recent data has shown the presence of neutrophilic inflammation in the lower airways. The current opinion is that airway inflammation is caused by the local, repeated mechanical trauma related to the intermittent airway occlusion typical of the disease. Another potential mechanism involves the intermittent nocturnal hypoxemia that through the phenomenon of the ischemia-reperfusion injury may induce the production of oxygen free radicals and therefore cause local and systemic inflammation. Finally, a state of low-grade systemic inflammation may be related to obesity per se with the pro-inflammatory mediators synthesised in the visceral adipose cells. Several authors stress the role of circulating and local inflammatory mediators, such as pro-inflammatory cytokines, exhaled nitric oxide, pentane and 8-isoprostane as the determinants of inflammation in OSA.

Prevalence of obstructive sleep apnoea in a sample of obese women: effect of menopause.

BACKGROUND: Obesity is a well known risk factor for obstructive sleep apnoea (OSA). Previous studies have investigated the prevalence of OSA among obese people, but a sample of women was rarely studied. OBJECTIVE: To describe the anthropometric and polysomnographic characteristics of a sample of obese women and investigate the effect of menopause on the prevalence of OSA. MATERIALS AND METHODS: Using a full-night polysomnography we studied a sample of 133 obese women with a body mass index (BMI) > or = 30 kg/m2. RESULTS: About 44% of our sample had a respiratory disturbance index (RDI) > or = 10. Neck circumference, BMI and age resulted the strongest predictors of RDI value. We also found that the prevalence of OSA was higher among post-menopausal women (67%) in comparison with pre-menopausal women (31%). Moreover, post-menopausal women had larger neck circumference and higher waist-to-hip circumference ratio (WHR). CONCLUSIONS: Among post-menopausal obese women the prevalence of OSA increases. We suggest that menopause could cause a different body fat distribution with an increase of fat in upper parts of the body and, consequently, with an increase of neck circumference.

Non-invasive pressure support ventilation in acute hypoxemic (non hypercapnic) respiratory failure. Observations in Respiratory Intermediate Intensive Care Unit.

BACKGROUND: Non-invasive positive pressure support ventilation (NIPSV). METHODS: In patients with acute hypoxaemic (PaO2/FiO2 &Mac178;100) non hypercapnic respiratory failure (ARF) admitted to a Respiratory Inter-mediate Intensive Care Unit of a general Hospital, between January 1993 and December 1997. RESULTS: In 21 selected patients (PaO2/ FiO2T0=82+/-9) NIPSV improved PaO2 in 13/21 patients (Group A) and did not improve in 8/21 patients (Group B) (PaO2/FiO2T1=154+/-25 in Group A vs PaO2/FiO2T1=106+/-7.5 in Group B, p=0.00001). Upon admission the two groups did neither significantly differ for blood gas values (PaO2/FiO2T0=84+/-9.6 in Group A vs 79.8+/-8.7 in Group B), nor for clinical status (APACHE II=19.8+/-5 in Group A vs 24.6+/-7 in Group B). Shorter duration of NIPSV in Group B patients (11.2+/-19.7 hrs vs 35.3+/-32.3 hrs in Group A, p=0.047), in spite of a rise in PEEP (9.3+/-2.3 in Group B vs 5.5+/-2.4 in Group A, p=0.003) and Pressure Support (18.7+/-1.8 in Group B vs 15+/-3.2 in Group A, p=0.004) was due to onset of conditions which required shifting from NIPSV to endotracheal intubation (ETI). OUTCOME: 8/21 patients were successfully treated by only NIPSV. 8/21 patients were intubated. 5/21 patients dead in RIICU; 1 month survival: 9/21 patients. Side effects: mask intolerance (3/21); skin necrosis (1/21); pneumothorax (1/21). CONCLUSIONS: NIPSV may be tried in ARF patients to improve PaO2 and avoid ETI.

Prescription of nCPAP and nBIPAP in obstructive sleep apnoea syndrome: Italian experience in 105 subjects. A prospective two centre study.

Nasal continuous positive airway pressure (nCPAP) is the current treatment of obstructive sleep apnoea syndrome (OSAS). The indications of bilevel pressure support ventilation (BIPAP PSV) in OSAS patients remain controversial. The purpose of this investigation was to verify the frequency of prescription of BIPAP PSV in a group of OSAS patients when CPAP was ineffective or not tolerated during titration. The study included 286 consecutive patients > or = 18 years of age referred to two Sleep laboratories for sleep related breathing disorders (SRBD) between December 1994 and November 1995. Of these, 130 patients were enrolled and 105 (88 males, 77 females) with moderate to severe OSAS completed the study and were finally analysed. After a full night diagnostic polysomnography (PSGD), patients had a second full night PSG under nCPAP (PSGT). If nCPAP was not tolerated, or failed to correct breathing abnormalities during sleep, a second PSGT was performed, using a BIPAP PSV. Our study shows that nCPAP (mean 8.5 +/- 2.0 cmH20) was considered a satisfactory therapy in 81 patients (77%). Twenty four (23%) required BIPAP PSV (mean IPAP 13.9 +/- 2.9 cmH20). We found the highest prevalence of BIPAP in patients with OSAS associated to obesity hypoventilation syndrome (OHS) (11 of 17) and in OSAS associated to chronic obstructive pulmonary disease (COPD) (nine of 16). Patients treated with BIPAP PSV were more obese and had a higher PaCO2 and sleep-related desaturations and a lower FEV1, FVC, FEV1/FVC and PaO2. In conclusion our study shows that CPAP therapy in the effective therapeutic option in the majority of patients with OSAS. There is a subset of patients with OSAS associated to COPD or to OHS in whom BIPAP PSV may be a better treatment modality.

Detection of Mycobacterium tuberculosis DNA in blood of patients with acute pulmonary tuberculosis by polymerase chain reaction and non-isotopic hybridisation assay.

The detection of Mycobacterium tuberculosis DNA in peripheral blood mononuclear cells (PBMC) by PCR and non-isotopic hybridisation assay was evaluated for the laboratory diagnosis of pulmonary M. tuberculosis infection. The PCR technique was based on the presence of IS6110, a DNA sequence specific for M. tuberculosis, and performed on PBMC from 30 patients belonging to the fifth group of the American Thoracic Society (ATS) classification of tuberculosis. The identification of amplification products was confirmed after electrophoresis by hybridisation with a non-isotopic probe in a DNA enzyme immunoassay (DEIA). Of the 30 blood samples studied by the PCR-DEIA technique, 26 gave positive results and four gave negative results. Blood samples from 30 subjects in a control group were negative by this technique. The data suggest that PCR-DEIA of blood may provide a sensitive, specific and useful means of diagnosing mycobacterial infection.

Increases in Cytosolic Ca2+ in Parsley Mesophyll Cells Correlate with Leaf Senescence.

The ability to maintain the cytoplasmic Ca2+ concentration ([Ca2+]cyt) at homeostatic levels has been examined during leaf senescence in detached parsley (Petroselinum crispum) leaves. Fluorescence ratiometric imaging of mesophyll cells isolated from parsley leaves at various senescence stages and loaded with the Ca2+ indicator fura-2 has revealed a distinct elevation of [Ca2+]cyt, which was positively correlated with the progress of leaf senescence. This initial increase of [Ca2+]cyt, which was first observed in cells isolated from 3-d-senescent leaves, occurred 1 d before or in parallel with changes in two established senescence parameters, chlorophyll loss and lipid peroxidation. However, the [Ca2+]cyt elevation followed by 2 d the initial increase in the senescence-associated proteolysis. Whereas the [Ca2+]cyt of nonsenescent cells remained at the basal level, the elevated [Ca2+]cyt of the senescent cells was a long-lasting effect. Experimental retardation of senescence processes, achieved by pretreatment of detached leaves with the cytokinin benzyladenine, resulted in maintenance of homeostatic levels of [Ca2+]cyt in cells isolated from 3-d-senescent leaves. These observations demonstrate for the first time to our knowledge a correlation between elevated [Ca2+]cyt and the process of senescence in parsley leaves. Such senescence-associated elevation of [Ca2+]cyt, which presumably results from a loss of the cell's capability to extrude Ca2+, may serve as a signal inducing subsequent deteriorative processes.

Legionellosis associated with artesian well excavation.

In October 1990 pneumonia due to Legionella pneumophila was diagnosed in two employees working in the area of Apulia, southern Italy, where artesian wells were in construction. Although the exposure to excavation has been associated with Legionnaires' disease, in our investigation the illness occurred only in those employees who were present when the water emerged from the ground under high pressure. On the basis of this report, water appears as the most likely reservoir of the organism and the main route of infection.

Effects of acetyl-L-carnitine oral administration on lymphocyte antibacterial activity and TNF-alpha levels in patients with active pulmonary tuberculosis. A randomized double blind versus placebo study.

Acetyl-L-carnitine (ALC), a drug for the treatment of ageing-related neuroendocrine dysfunctions, was orally administered--2 gm/day for 30 days--to 10 patients with active pulmonary tuberculosis (TBC). Lymphocyte-mediated antibacterial activity and serum levels of tumor necrosis factor (TNF)-alpha were evaluated before and after treatment, comparing the values with those of 10 TBC patients receiving placebo. Results show that by day 30, antibacterial activity remained unmodified or increased in ALC-treated subjects, while decreased in the placebo group. No influence of ALC on TNF-alpha levels was detectable. These data suggest that the host's immune responses to M. tuberculosis infection can be selectively modulated by drugs acting on the neuroendocrine axis.

Evaluation of phagocyte functions, inflammatory lymphokine activities and in vitro antibody synthesis in patients with active and chronic pulmonary tuberculosis.

In fourteen patients with pulmonary tuberculosis (TBC) (seven active and seven chronic cases) non-specific immunity and B cell function were evaluated. Polymorphonuclear cell (PMN) and monocyte chemotaxis, phagocytosis and killing were depressed to a different extent regardless of the disease status. Additionally, determination of lymphocyte-derived chemotactic factor and leukocyte inhibitory factor activities indicated a reduced production of these two lymphokines. This may also explain the impairment of phagocyte functions. Furthermore, the frequency of T cell subsets was slightly modified except for the increased number of CD25+ cells. The in vitro antibody response was analysed in a plaque-forming cell system using pokeweed mitogen (PWM) as a polyclonal activator and purified protein derivative (PPD) as a specific antigen. Results show that in patients with active TBC the anti-PPD antibody response was markedly enhanced, while in both groups of patients PWM-induced antibody synthesis was normal. These findings indicate several immune deficiencies related to phase activity which occur during the course of the disease.