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.

Detection of anti-lipoarabinomannan antibodies for the diagnosis of active tuberculosis.

SETTING: A serological test that contributes in diagnosing tuberculosis would aid patient management. OBJECTIVE: To evaluate MycoDot, a new commercially available serological test, for the detection of immunoglobulin G antibodies to lipoarabinomannan (LAM), a glycolipid common to mycobacteria. DESIGN: Serum samples from 102 non-human immunodeficiency virus (HIV)-infected patients with no previous history of tuberculosis and with suspected active pulmonary (66) and/or extra-pulmonary (36) tuberculosis were investigated; 50 HIV-negative healthy subjects, sputum culture-negative, tuberculin skin test negative and with no history of tuberculosis, were used as controls. RESULTS AND CONCLUSION: In 28 patients with microbiologically ascertained tuberculosis 25/28 serum samples were positive, whereas the test was negative in two patients with renal tuberculosis and in one with pulmonary tuberculosis. The remaining 74 serum samples were negative. The follow-up of these patients excluded a mycobacterial infection. Control subjects were negative. On the basis of our design, the MycoDot test, with its rapidity and degree of sensitivity, is suitable for routine use in laboratory diagnosis of both pulmonary and extrapulmonary tuberculosis.

The role of the expiratory phase in obstructive sleep apnoea.

The role of the expiratory phase in obstructive sleep apnoea (OSA) is not well known. The aim of our study was to verify the contribution of expiratory narrowing to apnoea in a group of OSA patients by evaluating the effects of short-term treatment with continuous positive airway pressure (CPAP), intermittent positive pressure ventilation (IPPV) and bi-level positive airway pressure (BIPAP). We studied a selected group of 10 OSA patients whose therapeutic pressure level of CPAP was at least 10 cm H2O. During CPAP therapy the mean apnoea/hypopnoea index (AHI) and oxyhaemoglobin desaturation index (ODI) decreased from 64.8 to 6.3 (P < 0.001) and from 58.5 to 6.1 (P < 0.001), respectively and mean nadir SAO2 increased from 62.0 to 91.6 (P < 0.001). None of the patients reached optimal setting (elimination of snoring, reduction of apnoeas and non-apnoeic desaturation events at least to 15 or less per hour of sleep and maintenance of oxygen saturation approximately 90%) during IPPV and two patients did not tolerate final IPAP pressure levels. When a critical level of EPAP (BIPAP) was applied in the same night to these patients, optimal setting was reached in all subjects. During BIPAP, mean AHI decreased from 64.8 to 7.4 (P < 0.001); ODI decreased from 58.5 to 7.6 (P < 0.001) and nadir SAO2 increased from 62.0 to 91.2 (P < 0.001). Our study confirms the essential role of a critical level of EPAP in successful ventilatory treatment in OSA, thereby indicating, in agreement with few previous studies, the critical role of end of expiratory occlusion in OSA pathogenesis.

Sleep-related breathing disorders in acute respiratory failure assisted by non-invasive ventilatory treatment: utility of portable polysomnographic system.

In the majority of patients admitted to an Intensive Care Unit with acute respiratory failure (ARF), the aetiology for ARF is quite evident. In a minority of patients no obvious aetiology is apparent at presentation. In this group a previously unrecognized sleep-related breathing disorder (SRBD) may be the cause of the ARF. In spite of clinical suspicion SRBD remains infrequently diagnosed in ARF also because the technology necessary for this type of diagnosis (polysomnography) is usually unavailable in Intensive Care Units. The aim of this study was to evaluate the utility of portable polysomnography system (PSGp) in a group of patients with ARF of unclear aetiology and with a clinical suspicion of SRBD. We studied a selected group of 14 patients (eight males, six females) admitted to an Intermediate Intensive care unit with varying degree of acute respiratory failure. Mean (SD) age was 57 (13) years, pH 7.28 (0.04), PaO2 5.6 (0.7) kPa), PaO2 (8.8 (1.6) kPa), Body mass index 42.7 (9.6) kg m(-2). The patients had no history of skeletal, neuromuscular or cardiovascular disease. None of them had a history of overt chronic lung diseases or had obvious respiratory tract infections. They were submitted to cardiac and respiratory functional evaluation and to nightly PSGp (VITALOG HMS 5000, Respironics Inc., Redwood City, CA, U.S.A.) which was performed in an intermediate intensive care unit. Ten subjects had obstructive sleep apnoea-hypopnoea syndrome (OSAS), with mean respiratory disorder index h(-1) (RDI) 60.1 (25.9) [in five associated with obesity-hypoventilation syndrome (OHS)]; two had central sleep apnoea with mean RDI 45 (28.3) (one with hypothyroidism and one with cerebral multiple infarctions and right hemidiaphragmatic paralysis) and two had OHS with mean RDI 12.5 (3.5). Nocturnal hypoventilation was present in almost all patients. Continuous positive airway pressure (CPAP) was effective in three patients. Eight patients needed to be treated with BILEVEL (BiPAP, Respironics Inc.) airway positive pressure in timed or spontaneous/timed modes. Two patients required intubation and mechanical ventilatory treatment. In one patient with hypothyroidism was sufficient to institute hormonal therapy. Our study shows that acute respiratory failure due to SRBD is not exceptional in an Intermediate Intensive Care Unit and that if clinical suspicion is strong, portable polysomnography may yield diagnostic confirmation and help in establishing appropriate treatment and in avoiding the invasive ventilatory treatment.

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.

Autonomic dysfunction in normotensive awake subjects with obstructive sleep apnoea syndrome.

Obstructive sleep apnoea syndrome (OSAS) is associated with systemic arterial hypertension and cardiac arrhythmias and may lead to cardiovascular complications. Dysfunction of the autonomic nervous system (ANS) may play a role in the development of cardiovascular complications. The aim of this work was to study the ANS by spectral analysis of the heart rate variability (HRV) at rest and after stress (head-up tilt test) in a group of normotensive awake OSAS subjects. We studied 22 males with OSAS, aged 47.6 +/- 13.1 yrs, with a body mass index (BMI) 35.6 +/- 7.7 kg.m-2 and blood systolic and diastolic pressure (BSP and BDP, respectively) of 128 +/- 16 and 80 +/- 9 mmHg. Nineteen healthy males were studied as controls. Autonomic investigations were performed using the computerized power spectral analysis of HRV with autoregressive modelling which identifies low frequency (LF), as a marker of sympathetic activity and high frequency (HF), as a marker of vagal activity. OSAS patients showed greater sympathetic activity (LF) at rest than normal subjects, and an abnormal response to the head-up tilt test compared to control subjects. Five OSAS patients behaved like control subjects. Comparison of the functional parameters between these five OSAS patients and the other 17 OSAS patients showed a statistically significant difference for only basal arterial carbon dioxide tension (Pa,CO2) and minimal nocturnal oxyhaemoglobin (HbO2) saturation (NADIR). Our study shows autonomic nervous system dysfunction in patients with obstructive sleep apnoea syndrome, which may have facilitated a pathophysiological link with the cardiovascular complications observed in these patients.

Depressed baroreceptor reflex in patients with obstructive sleep apnea (OSA).

In this study we evaluated the cardiovascular autonomic function in twenty-five OSA patients and in twenty-five control healthy subjects, by computerized spectral analysis of R-R interval variation at rest and during orthostatism by head-up tilt maneuver to up-right position (80 degrees) as a sympathetic provocation. The results of our study show that most patients affected by OSA have a sympathetic overactivity and a decreased baroreflex response in comparison with normal subjects. The method here described is simple, objective and very sensitive and may be utilized to discover early signs of an autonomic dysfunction consequent to OSA leading to cardiovascular complications of the late stage of the disease.

Functional assessment of airways bronchoconstriction with nebulized acetyl salicylic acid.

The aim of our study was to verify the functional modifications affecting central and peripheral airways during bronchoconstriction induced by aerosolized aspirin, so as to better understand the pathophysiologic mechanisms of the asthmatic crises in A.S.A. sensitive patients. The preliminary results were presented of a study carried out o 12 asthmatic A.S.A. sensitive patients, 7 of whom were females and 5 males, between the ages of 22 and 57 years. A.S.A. sensitivity was found in their medical history, in some cases, it had been confirmed by oral A.S.A. challenge. Among these patients, 6 were also affected by nasal polyposis. The method used was recently described by Bianco et al. although slightly modified by us: a fresh aqueous solution (18%) of A.S.A. -L is diluted 1:3 in saline; 4 ml of this solution is transferred to a glass nebulizer activated by a small compressor. The patients underwent treatment for 60 sec, during which a dose of approximately 1,8 mg of A.S.A. was inhaled, corresponding to about 40 mg of aspirin taken orally. In comparison with the reactions induced by oral challenge, those obtained with this treatment are easier, faster and confined only to the respiratory system. Before giving A.S.A. to the patients, control tests using saline aerosol were done. The functional assessment was performed under basal conditions, and 1, 15, 30, 60, 90 and 120 minutes following administration of A.S.A. since bronchoconstriction caused by nebulized A.S.A. usually reaches peak values between the 60th and 90th min. after which it gradually decreases over the following two hours. Our results show that, though A.S.A. induced bronchoconstriction prevails at large airways, it also influences the distal tracts of the tracheobronchial tree, since both SRAW, FEV1 and Vmax50C are modified at the same time.

Asthma relieved by acetylsalicylic acid and nonsteroid anti-inflammatory drugs.

The authors report 2 typical asthmatic cases in whom the administration of acetylsalicylic acid (ASA) and nonsteroid anti-inflammatory drugs (NSAID) resulted in bronchodilatation. 500 mg of ASA were administered intravenously to 1 patient and the other was treated with ASA, indomethacin, noramidopyrine intravenously and acetaminophen orally during a bronchospastic attack. FEV1 and SRAW were measured before and after drug administration. The test was repeated with placebo (physiological saline). FEV1 increased rapidly after ASA and NSAID administration. Although the pathogenesis of asthma reversed by aspirin is not entirely clear, the authors suggest an alteration of sensitivity of the cyclo-oxygenase enzyme due to the inhibitory action of ASA and NSAID.

Protective effect of Duovent on bronchospasm induced by carbachol in comparison with each of its components.

The protective effect on bronchospasm, induced by carbachol, of 2 puffs of fenoterol (200 micrograms), ipratropium bromide (80 micrograms) and Duovent (200 micrograms fenoterol + 80 micrograms ipratropium bromide) was compared in a group of 12 asthmatic patients. The double-blind study was always performed at the same time of day, 2 and 5 h after premedication, on 4 consecutive days. After the 1st day, when placebo was given, the drugs were administered randomly. As regards PD20 FEV1 (dose of carbachol necessary to determine a 20% decrease in FEV1), Duovent was found to be the most active drug. A very clear difference was seen 2 h later, not only compared to fenoterol (PD20 placebo, means +/- SD: 90.8 +/- 93.2 micrograms; PD20 Duovent: 1,876.5 +/- 1,103.5 micrograms; PD20 fenoterol: 324.3 +/- 220.7 micrograms) but also with ipratropium bromide (PD20: 1,215.8 +/- 950 micrograms). After 5 h, the three treatments maintained a significant action, but the efficacy of Duovent, while significantly greater than that of fenoterol, was very similar to that of ipratropium (PD20 placebo: 78.4 +/- 92.6 micrograms; PD20 fenoterol: 134.6 +/- 138.2 micrograms; PD20 ipratropium bromide: 295.4 +/- 337 micrograms; PD20 Duovent: 286.7 +/- 181.2 micrograms).