Roger Sergysels

Domestic endotoxin exposure and clinical severity of asthma

Endotoxins are potent pro‐inflammatory substances present in several natural environments and in commercial house dust extracts. To investigate the possible effect of chronic endotoxin exposure on asthma, 28 patients with perennial chronic asthma (20 allergic to house dust mite and eight intrinsic asthmatics) were evaluated during a 4‐month period (lung function, clinical and immunological criteria). At the same time, two house dust samples were collected from each patients home to determine total house dust weight (mg/m2), endotoxin concentration and house dust mite antigen content (evaluated indirectly by guanine content with HPLC method). The mean (± s. d.) endotoxin concentration, as measured by quantitative Limulus assay was 2.59 (± 3.41) ng/mg house dust, ranging from 0.12 to 20 ng/mg. The mean guanine content was 0.13 (± 0.16) mg/100 mg house dust. There was no correlation between endotoxin and house dust mite concentrations. Patients were compared according to the low or high grade exposure to dust, endotoxins and guanine. Compared with patients with low grade (≤ 5.6 ng/ml) exposure, subjects exposed to high endotoxin concentrations (> 5.6 ng/ml) showed a significant increase in dyspnea (median 2.6 vs 3.3; P<0.05) and treatment (median 14 vs 44.3; P<0.01) scores, oral corticosteroid (median 0.0 vs 13.5 mg/24 hr; P<0.01) and β2‐mimetics (median four vs eight puffs/day; P<0.01) intake, and a significant decrease in FEV1/FVC (median 84.5 vs 67% of predicted value; P<0.01). In contrast, no differences were found between the two groups exposed to low (< 0.07 mg/100 mg house dust) and high (≥ 0.07 mg/100 mg house dust) concentrations of guanine, respectively. We conclude that endotoxins are present in normal domestic environment and could have a deleterious effect on the chronic asthmatic disease.

Clinical use of the meropenem-clavulanate combination for extensively drug-resistant tuberculosis.

Mycobacterium tuberculosis strains resistant to almost all available anti-tuberculosis drugs are an increasing threat to public health worldwide. Among existing drugs with potential antimycobacterial effects, the combination of meropenem with clavulanate has been shown to have potent in vitro bactericidal activity against extensively drug-resistant tuberculosis (XDR-TB). To explore its potential clinical efficacy, a meropenem-clavulanate-containing salvage regimen was started in six patients with severe pulmonary XDR-TB, in association with the only one or two remaining active second-line drugs. Encouraging preliminary data are detailed and discussed.Mycobacterium tuberculosis strains resistant to almost all available anti-tuberculosis drugs are an increasing threat to public health worldwide. Among existing drugs with potential antimycobacterial effects, the combination of meropenem with clavulanate has been shown to have potent in vitro bactericidal activity against extensively drug-resistant tuberculosis (XDR-TB). To explore its potential clinical efficacy, a meropenem-clavulanate-containing salvage regimen was started in six patients with severe pulmonary XDR-TB, in association with the only one or two remaining active second-line drugs. Encouraging preliminary data are detailed and discussed.

Randomized trial comparing induction chemotherapy versus induction chemotherapy followed by maintenance chemotherapy in small-cell lung cancer. European Lung Cancer Working Party.

PURPOSE AND METHODS The European Lung Cancer Working Party (ELCWP) performed a randomized trial with the primary end point to determine if maintenance chemotherapy with 12 courses of etoposide (120 mg/m2 on days 1 and 3) and vindesine (3 mg/m2 on day 3) could improve progression-free survival in small-cell lung cancer (SCLC) patients who responded to six courses of induction chemotherapy with ifosfamide, etoposide, and an anthracycline (doxorubicin or epirubicin). RESULTS Among 235 eligible patients initially registered, 91 were randomized to receive maintenance therapy, including seven patients who were no longer responding. Among 84 randomized responders, progression-free survival was significantly improved (P = .003) by maintenance therapy, with median durations (maintenance v follow-up) of 25 versus 12 weeks after the second randomization, but survival was not significantly increased (P = .10), with median durations of 48 and 38 weeks. However, in a multi-variate analysis that took into account disease extent, maintenance therapy, Karnofsky performance status (PS), and absolute dose-intensity (ADI) of anthracycline given during induction, limited disease (LD) and maintenance were found to be independent positive predictors of survival. CONCLUSION We conclude that maintenance chemotherapy in responding patients is beneficial in SCLC.

Sleep efficiency during sleep studies: results of a prospective study comparing home‐based and in‐hospital polysomnography

To date, the clinical use of unattended home‐based polysomnography (PSG) is not recommended. To assess whether sleep efficiency is better at home, we have performed a prospective, crossover, single‐blind study comparing unattended home‐ versus attended in‐hospital PSG in a population referred for high clinical suspicion of obstructive sleep apnoea syndrome (OSA). Within 2 weeks, all the patients underwent both PSG performed by the same sleep technician, which were analysed by another blinded technician. Payments for each procedure were also calculated. Sixty‐six patients (mean age: 49 ± 13 years; mean body mass index: 30 ± 7; mean Epworth Sleepiness Scale: 10 ± 5) were included. The quality of recordings was poor in 1.5% of the attended PSG versus 4.7% for unattended PSG (P = 0.36). Sleep efficiency at home was better (82% versus 75%, P < 0.001), and sleep duration longer (412 min versus 365 min, P < 0.001). Sleep latency was also shorter at home (28 min versus 45 min, P = 0.004), and patients spent more time in rapid eye movement sleep (19% versus 16%, P = 0.006). Apnoea–hypopnoea index (23 versus 26, P = 0.08) was similar at home and in the sleep lab. Sixty‐seven per cent of patients preferred home‐based PSG. PSG payment was also lower at home (268 Euros versus 1057 Euros). We conclude that home‐based PSG is associated with a better sleep efficiency. It also appears as feasible and reliable in patients with high preclinical suspicion for OSA. It is also more comfortable for the patients whose sleep efficiency is better and allows cost saving related to the absence of hospitalization.

Phase II randomized trial comparing high-dose cisplatin with moderate-dose cisplatin and carboplatin in patients with advanced non-small-cell lung cancer. European Lung Cancer Working Party.

PURPOSE A phase II randomized trial was conducted in patients with advanced non-small-cell lung cancer (NSCLC) to determine if the combination of moderate-dose cisplatin and carboplatin was active (primary end point) and could avoid the long-term limiting (renal, auditive, neurologic) toxicity of high-dose cisplatin, which prevents prolonged administration (secondary end point). PATIENTS AND METHODS One hundred twenty-one patients, registered between April 1990 and September 1991, were randomized to receive high-dose cisplatin (120 mg/m2 intravenously [IV] on day 1) or a combination of moderate-dose carboplatin (200 mg/m2 IV on day 1 and moderate-dose cisplatin (30 mg/m2 IV on days 2 and 3). One hundred nine patients were eligible: 56 in the cisplatin arm and 53 in the combined arm; 52 and 47, respectively, were assessable for response. All had stage IV disease (or stage IIIB with pleural effusion) and none had received prior chemotherapy. RESULTS There was a 23% objective response rate to cisplatin (23% of the eligible patients) and a 22% response rate to cisplatin plus carboplatin (21% of the eligible patients). The overall survival rate was not significantly different between the two study arms, but responders in the combined arm survived significantly longer than those in the high-dose cisplatin arm (respective median survival durations, 66 and 30 weeks). Although there was no difference between the arms for alopecia, emesis, and leukopenia, the combined arm was significantly associated with more thrombocytopenia (although rarely severe) and, more importantly, with less renal (19% v 36%), auditive (4% v 16%), and neurologic (0% v 16%) toxicity of any grade. CONCLUSION The regimen combining moderate-dose cisplatin and carboplatin was active against advanced NSCLC and significantly less toxic than high-dose cisplatin.

Cardiopulmonary adaptation to exercise in coal miners

Twenty-six coal miners, without associated functional chronic obstructive lung disease (COLD), assessed by normal airway resistance, were divided into three groups: (1) Group C, normal X-ray; (2) Group S1, micronodular silicosis; and (3) Group S2, complicated silicosis. All subjects were evaluated while at rest and during exercise. Significant lung volume reduction was observed in the S2 Group only. Blood gases, pulmonary pressure, and cardiac output were found to be within the normal range for all three groups when at rest. The pulmonary pressure and pulmonary vascular resistance were higher, however, for the S1 and S2 Groups when compared to the C Group. During exercise, pulmonary hypertension was observed in 50% of teh patients with complicated silicosis. When all data (N = 26) were included, the high values for pulmonary pressure and pulmonary vascular resistance correlated well with the loss in vital capacity (VC) and the decrease in forced expiratory volume in 1 sec (FEV 1.0). From the initial 26 patients, 19 were selected on the basis of their normal airway resistance and FEV 1.0/VC ratio. This selection did not alter the differences noted for the pulmonary pressure and total pulmonary vascular resistance, which previously existed between the groups, even though the correlations were not statistically significant. We conclude that silicosis without associated COLD leads to mineral hemodynamic impairment at rest and during exercise, and that airway resistance does not detect impairment of flow as effectively as FEV 1.0 reduction. The increased pulmonary vascular resistance observed, especially in complicated silicosis, may be best explained by the loss of lung parenchyma and possible impairment of small airways.

Thoracoabdominal Motion during Chest Physiotherapy in Patients Affected by Chronic Obstructive Lung Disease

In 11 patients suffering from chronic obstructive lung disease, thoracoabdominal movements were monitored with magnetometers during various breathing manoeuvres directed by the chest physiotherapist. The signals derived from the magnetometers and the mouth flow were analysed in order to pick up paradoxical movements of one or the other compartment of the chest wall. In contrast to what was observed during spontaneous breathing, especially abdominodiaphragmatic breathing induced in most of the subjects paradoxical movements. The practical importance of accurate monitoring of thoracoabdominal motion during chest physiotherapy is stressed.

Expiratory flow limitation during exercise in COPD: detection by manual compression of the abdominal wall

Manual compression of the abdomen (MCA) during spontaneous expiration is a simple method for the detection of flow limitation in the chronic obstructive pulmonary disease (COPD) patients during resting breathing, based on comparison of flow/volume curves obtained during MCA with that of the preceding control breath. It was assessed whether this nonstandardized technique is also feasible during exercise. MCA was performed during resting breathing and constant-exercise work at one- and two-thirds maximal mechanical power output (W′max) in six normal subjects and 12 COPD patients. Changes in end-expiratory lung volume (EELV) were also studied. With the aid of inspection, abdominal palpation and lung auscultation, MCA could always be applied during expiration. Flow limitation was never detected in the six normal subjects, whereas four of the COPD patients were flow limited at rest, seven during exercise at one-third W′max and nine during exercise at two-thirds W′max. Expiratory flow limitation detected by MCA was always associated with an increase in EELV during exercise, indicating dynamic hyperinflation occurrence or increase. It is concluded that manual compression of the abdomen is a very simple and reliable method for the detection of flow limitation during exercise.

Cyclic haemodynamic and arterial blood gas changes during Cheyne-Stokes breathing

A 74-year-old patient presented with congestive heart failure and continuous periodic breathing. Left ventricular ejection fraction was 20% and the lung-to-brain circulation time was prolonged to 35 s. We report on the phasic changes of the patients arterial blood gas tensions and on the periodic fluctuations of pulmonary artery pressures and cardiac output that we observed during Swan-Ganz catheterisation.

Effect of anti-asthmatic drugs on the response to inhaled endotoxin

BACKGROUND Endotoxin is a pro-inflammatory agent contaminating the dust that has been associated with the risk to develop pulmonary diseases. There is no data on the protective efficacy of anti-asthmatic drugs on the response induced by inhaled endotoxin in human. METHODS Twelve mildly asthmatic subjects were submitted weekly to bronchial challenge tests with 20 microg endotoxin. The response was evaluated by the changes in FEV1, blood cells count, neutrophils activation (measured with the luminol-enhanced chemiluminescence) and blood concentration in the acute phase proteins, C-reactive protein (CRP) and haptoglobin. In a double-blind randomized cross-over placebo-controlled design, a single dose each of 500 microg beclomethasone dipropionate, 200 microg salbutamol, and 50 microg salmeterol were administered 30 minutes before the endotoxin challenge test. RESULTS The 20-microg endotoxin challenge test induced a significant decrease in FEV1 and luminol-enhanced chemiluminescence (P < .001 and <.05, respectively). There was an increase in the blood neutrophils count (P < .05), in CRP (P < .02) and in haptoglobin (P < .03) concentrations. Pretreatment with beclomethasone dipropionate did not have any significant effect on the response to inhaled endotoxin. Salbutamol and salmeterol completely prevent the FEV1 decline due to their potent bronchodilatation activity. Salmeterol and salbutamol did not have any significant effect on the blood inflammation induced by endotoxin inhalation. CONCLUSION The bronchodilating properties of beta2-agonists prevent the lung function response to inhaled endotoxin. When given in a single dose, an inhaled corticosteroid does not have protective activity on the endotoxin-induced blood inflammation.