[Pulmonary hypertension associated with disorders of the respiratory system]. / Hypertension pulmonaire des affections respiratoires chroniques.

Pulmonary hypertension associated with disorders of the respiratory system is defined by a pulmonary artery mean pressure above 20 mmHg at rest in stable disease. The most frequent form of precapillary pulmonary hypertension is associated with chronic obstructive pulmonary disease, because of its high prevalence. Pulmonary vascular remodeling occurs in the small pulmonary arteries and is due mainly to chronic alveolar hypoxia. Pulmonary hypertension associated with disorders of the respiratory system is usually mild to moderate, with resting pulmonary artery mean pressure ranging between 20 and 35 mm Hg. It may increase markedly during sleep, exercise or exacerbation of respiratory failure, however. Abrupt postload elevation can lead to right heart failure, an indisputable indicator of prognosis. Because the symptoms of pulmonary hypertension are minimal relative to those of the chronic hypoxic lung disease, noninvasive diagnosis is difficult, particularly in patients with chronic obstructive pulmonary disease. Oxygen therapy (at least 16 h/day) is currently the best treatment for this type of pulmonary arterial hypertension.

[Physiological functional tests to evaluate pulmonary arterial hypertension]. / Explorations fonctionnelles dans l'hypertension artérielle pulmonaire.

INTRODUCTION: Pulmonary arterial hypertension (PAH) is a rare and complex disease, which requires careful diagnostic evaluation. STATE OF THE ART: Most patients have a mild decrease in lung volumes and a moderate decrease in carbon monoxide transfer factor. Mild to moderate arterial hypoxaemia, is often present, associated with a mild respiratory alkalosis. When hypoxaemia is severe, it may represent an intracardiac shunt. Right heart catheterisation is required to confirm the diagnosis and in most cases shows a significant elevation of pulmonary artery pressure due to an increase in pulmonary vascular resistance. The haemodynamic profile and the response to an acute pulmonary vasodilator challenge are determinants of prognosis. Finally, exercise capacity which is usually assessed by the six minute walk test provides an overall functional measure of disease severity, response to therapy, and progression. PERSPECTIVES: Functional evaluation of the heart using echocardiography will play an increasing role in the evaluation of PAH. CONCLUSIONS: Physiological measurements in PAH have several objectives. They form part of the diagnostic definition, allow the exclusion of other conditions and are tools for the assessment of severity, prognosis and response to therapy.

Phase II randomised trial comparing docetaxel given every 3 weeks with weekly schedule as second-line therapy in patients with advanced non-small-cell lung cancer (NSCLC).

BACKGROUND: Taxotere (docetaxel) at the dose of 75 mg/m(2) every 3 weeks is a standard therapy for pretreated non-small-cell lung cancer (NSCLC). The aim of this study was to evaluate the safety profile of two schedules of docetaxel administration (every 3 weeks versus weekly) in patients with pretreated NSCLC. PATIENTS AND METHODS: From February 2000 to February 2001, 125 patients with locally advanced or metastatic NSCLC were randomised after failure of a previous platinum-based regimen to receive either docetaxel 75 mg/m(2) administered every 3 weeks (Dq3w) or docetaxel 40 mg/m(2) given weekly for 6 weeks followed by 2 weeks of rest (Dqw). Safety evaluations focused on grade 3-4 neutropenia, febrile neutropenia, nausea-vomiting and asthenia. RESULTS: Patients' characteristics were well balanced between arms. The most common National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3-4 toxicity was neutropenia, which occurred in 48.4% of Dq3w patients versus 15.9% of Dqw patients (P=0.001). In addition, febrile neutropenia were observed in 6.5% of patients in Dq3w versus 0% in Dqw. Grade 3-4 asthenia was more frequent in Dqw. Other non-haematological toxicities were very rare. Regarding efficacy, there was a trend towards a better disease control rate in Dq3w: 32.2% versus 25.4% in Dqw. Median time to progression and survival were rather similar in both arms, respectively: 2.1 months (range 2-3.2) and 5.8 months (range 4.0-7.0) in Dq3w and 1.8 months (range 1.6-2.3) and 5.5 months (range 3.7-6.6) in Dqw. CONCLUSIONS: While both schedules had a favourable safety profile, a significant lower rate of severe neutropenia was observed in the weekly arm. Both regimens had similar efficacy. The weekly regimen could be considered as a good alternative for patients at risk of severe neutropenia.

Randomised, multicentre phase II study assessing two doses of docetaxel (75 or 100 mg/m2) as second-line monotherapy for non-small-cell lung cancer.

BACKGROUND: The survival benefit associated with first-line chemotherapy in advanced lung cancer led to the need for second-line chemotherapy. Docetaxel (Taxotere) has proven efficacy in both settings. This study evaluated the safety and efficacy of two doses of docetaxel in patients with non-small-cell lung cancer who had failed first-line platinum-based chemotherapy. PATIENTS AND METHODS: In total, 182 patients from 24 French centres were randomised and treated with either docetaxel 75 mg/m(2) (arm A) or 100 mg/m(2) (arm B) every 3 weeks. Baseline characteristics were well balanced, except more patients in arm A had metastatic disease (91.4% versus 78.7%) and therefore the median number of sites involved for arm A was three compared with two for arm B. RESULTS: Median time to treatment failure was 1.34 months [95% confidence interval (CI) 1.28-1.64] for arm A and 1.64 months (95% CI 1.34-2.62) for arm B. Median overall survival was 4.7 months (95% CI 3.8-5.9) for arm A versus 6.7 months (95% CI 4.8-7.1) for arm B. According to a blinded expert panel, disease control was achieved in 35 (43.8%) patients in arm A and 39 (49.4%) patients in arm B. More patients in arm B experienced grade 3-4 neutropenia (B: 72.7% versus A: 44.0%), asthenia (B: 20.2% versus A: 10.8%) and infection (B: 6.7% versus A: 2.2%). Three treatment-related deaths were reported in each arm. CONCLUSIONS: The optimal docetaxel dosage in this second-line setting is 75 mg/m(2), as it has a more favourable safety profile and on balance a similar efficacy to the 100 mg/m(2) dose.

[Role of gastroesophageal reflux in asthma in infants and young children]. / Rôle du reflux gastro-oesophagien dans l'asthme du nourrisson et du jeune enfant.

Gastroesophageal reflux (GER) occurs more frequently in asthmatic children than in general population. Esophageal pH recording data may be somewhat particular. The debate on GER increasing bronchial obstruction or GER being a parallel phenomenon remains controversial. Hypotheses are: acid microaspirations giving bronchospasm, vagally-transmitted reflex, or more probably coexisting phenomena. Pulmonary contamination is rarely seen during esophageal scintigraphy. Asthma symptoms are rarely clearly correlated to acid reflux episodes in pH-recording studies. However the esophageal acid infusion test may increase bronchial obstruction in adult asthmatics. Basically, when should one seek GER in asthmatic children? Many authors keep this for asthmatic children not responding to conventional treatment, also keeping in mind that GER-specific therapy efficacy is often difficult to appreciate in such patients. Briefly, one may speculate that GER improves with bronchodilator treatment in most cases.

"Natural history" of pulmonary hypertension in a series of 131 patients with chronic obstructive lung disease.

The prognostic value and the evolution of pulmonary hypertension (PH) in patients with markedly hypoxemic chronic obstructive pulmonary disease (COPD), treated or not with long-term oxygen therapy (LTOT), has been extensively investigated. However, little is known in patients with mildly or moderately hypoxemic COPD not requiring LTOT. Therefore, we assessed the evolution of pulmonary hemodynamics in 131 patients with stable COPD by performing two right heart catheterizations at a mean (+/- SD) time interval of 6.8 +/- 2.9 yr. At inclusion (T0), no patient had PH (i.e., the mean pulmonary artery pressure [Ppa] at rest was < 20 mm Hg). Group 1 included 55 patients without exercising PH and group 2 included 76 patients with exercising PH, defined by a pulmonary arterial pressure (Ppa) > 30 mm Hg during a steady-state 40-W exercise. Group 2 patients compared with group 1 patients had a significantly higher resting Ppa (16 +/- 3 mm Hg versus 14 +/- 2 mm Hg, p = 0.001). At the second catheterization, 33 (25%) patients (9 of 55 in group 1, 24 of 76 in group 2, p = 0.048) showed a resting Ppa > 20 mm Hg, but PH was generally mild, ranging from 20 to 42.5 mm Hg. The mean Ppa at second evaluation was 16 +/- 5 mm Hg in group 1 and 19 +/- 7 mm Hg in group 2 (p = 0.01). The patients who developed resting PH at the second catheterization (T1) had higher resting and exercising Ppa (p = 0.001 and p = 0.002, respectively), and significantly lower resting and exercising Pa(O(2)) (p = 0.005 and p = 0.012, respectively) at T0. Logistic regression analysis showed that resting and exercising Ppa were independent predictors (at T0) for the subsequent development of PH (p = 0.029 and p = 0.027, respectively). The patients who developed resting PH (T1) had a significantly worsening of Pa(O(2)) (from 63.5 mm Hg at T0 to 60 mm Hg at T1, p = 0.047), whereas the Pa(O(2)) as a mean was stable in the remainder (69.5 mm Hg at T0 and T1). These results show the following. The progression of Ppa over time in patients with COPD with mild to moderate hypoxemia is rather slow, the average change for the group as a whole being of + 0.4 mm Hg/yr. Only about 25% of patients with COPD with mild to moderate hypoxemia and without resting PH at the onset will develop PH during a 6-yr follow-up. The patients with exercising PH at the onset have a significantly increased risk of developing PH over time. Only resting and exercising Ppa at the onset are independently related to the subsequent development of PH. However, in individual cases, the models of linear or logistic regression do not allow a pertinent prediction of the level of Ppa or the presence of PH at the second right heart catheterization.

Regulation of endothelin-1 at rest and during a short steady-state exercise in 21 COPD patients.

Endothelin-1 (ET-1) is a vasoconstrictive peptide which may play a relevant role in the pathogenesis of pulmonary hypertension (PH) in COPD patients. We assessed the correlations of plasmatic ET-1 levels with pulmonary function data, arterial blood gases and pulmonary haemodynamics in 21 COPD patients with moderate to severe airway obstruction (FEV1: 1.19+/-0.49 l, mean+/-SD). There were 11 hypoxemic patients (PaO2 <65 mmHg). Six patients had resting PH (mean pulmonary artery pressure >/=20 mmHg). Eight patients had exercising PH (PAP >/=30 mmHg) during a short (6 min) 30 W steady state exercise. At rest, arterial ET-1 levels were significantly higher in COPD patients with hypoxemia when compared to those without hypoxemia (16.6+/-2.7 vs. 12.5+/-3.9 pM/l, P=0.02) and in COPD patients with PH when compared to those without PH (16.5+/-3.4 vs. 13+/-3.9 pM/l, P=0.04). Resting arterial ET-1 levels were negatively correlated with PaO2 (r=-0.45, P=0.05). At rest, the differences between mixed venous and arterial ET-1 levels were positively correlated with FEV1 (r=0.54, P=0.024). At exercise, the mean arterial ET-1 level was not significantly different from the mean resting ET-1 level (13.8+/-3.4 vs. 13.3+/-4 p M/l, NS). There were eight COPD patients who had decreasing arterial ET-1 levels between rest and the end of a 6 min exercise, and six COPD patients who had increasing arterial ET-1 levels. These variations of arterial systemic ET-1 levels from rest to exercise were negatively correlated with FEV1 (r=-0.66, P=0.01). We conclude that in COPD patients (1) at rest, arterial ET-1 levels are increased in hypoxemia or pulmonary hypertension and (2) at rest or during exercise, the turn-over of ET-1 may be dependent of the degree of the bronchial obstruction.

A phase II trial of radiochemotherapy with daily carboplatin, after induction chemotherapy (carboplatin and etoposide), in locally advanced nonsmall-cell lung cancer: final analysis.

PURPOSE: To evaluate feasibility and efficacy of concomitant radiochemotherapy (CRCT) in Stage IIIB nonsmall-cell lung cancer (NSCLC), two induction chemotherapy cycles combining etoposide and carboplatin were first delivered, followed by CRCT with daily radiation fraction in association with carboplatin. METHODS AND MATERIALS: Forty patients with biopsy-proven, locally advanced unresectable nonmetastatic NSCLC were enrolled. Induction chemotherapy consisted of two cycles (day 1 and day 28) of etoposide (VP16:100 mg/m2, days 1 to 3) and carboplatin (CBDCA:350 mg/m2, day 1). Irradiation starting at day 56, delivered 66 Gy in 2 Gy daily fraction, 5 days a week, along with a daily dose of CBDCA (15 mg/m2) given intravenously 2 to 4 h before radiation. In nonprogressive patients under induction chemotherapy, two additional cycles of VP16-CBDCA were administered 4 weeks after the completion of CRCT. RESULTS: Out of the 40 patients enrolled (38 males, 2 females), 37 (93%) received induction chemotherapy as scheduled, with 38% Grade 3-4 hematological toxicity. Response rate to induction chemotherapy was 11% (4/37). No tumor became resectable. CRCT was delivered to 32 of these 37 patients, with full doses given to 91% of them. Clinical and hematological Grade 3-4 toxicity rates were 21 and 13%, respectively. Additional chemotherapy was delivered in 12 of 26 nonprogressive patients. At final evaluation, performed 3 months after the end of CRCT, 38% of 26 evaluable patients were responders (4 complete and 6 partial), leading to a 25% (10 of 40) overall objective response rate. Of these 10 responders, 8 became responders after CRCT only. Overall, the 1-year local control rate was 28% (11 of 40). The median survival time was 9 months and the 1-year and 2-year overall survival rates were 38 and 15%, respectively. Thirty-six patients died from local progression (25 patients), distant metastasis (9 patients), or pulmonary fibrosis (2 patients). CONCLUSION: Concomitant CRCT with CBDCA is feasible with acceptable induction chemotherapy-related toxicity and a 1-year local control rate of 28%. Response rate to induction chemotherapy was low and better chemotherapy combination should be used to reduce distant failure probability and to improve local response rate before CRCT.

[Is chemotherapy with cisplatin useful in non small cell bronchial cancer at staging IV? Results of a randomized study]. / La chimiothérapie comportant du cisplatine est-elle utile dans le cancer bronchique non microcellulaire au stade IV? Résultats d'une étude randomisée.

The benefit of chemotherapy for patients with disseminated non small cell lung cancer (NSCLC) is controversial. The introduction of cisplatinum in the combination chemotherapy for NSCLC gave rise to higher response rates. To study the question of the usefulness of cisplatinum-based chemotherapy in disseminated NSCLC we conducted a prospective randomized trial comparing best supportive care to vindesine + cisplatin. Between December 1985 and March 1988, 49 patients with stage IV NSCLC were enrolled. Of the 46 eligible patients 24 were in the chemotherapy group and 22 in the best supportive care group. The treatment groups were not significantly different in terms of age, performance status, histology. Toxicity on the chemotherapy arm grade 3 or more was observed in 17.5% for neutropenia, in 8.75% for vomiting. There was one death related to treatment. The overall response rate in the chemotherapy group was 41.7%. Patients of the chemotherapy group had a median survival time of 199 days and the patients of the best supportive care group had a median survival time of 73 days. The difference in survival is highly significant (p less than 0.001).

[Gastroesophageal reflux in asthmatic and chronic bronchitis patients]. / Reflux gastro-oesphagien chez les asthmatiques et les bronchitiques chroniques.

To determine the relationship between gastroesophageal (GE) reflux and pulmonary disease, we studied 21 asthmatics, 30 chronic bronchitics, 6 patients with GE reflux and no pulmonary symptoms, and 10 control subjects; GE reflux was diagnosed by pH monitoring and GE scintiscanning. Frequency of GE reflux in the asthmatics was 57%; in chronic bronchitis it was 56%. Pulmonary function tests did not show any differences between patients with or without reflux. The GE reflux episodes were more numerous but shorter in asthmatics than in chronic bronchitis. Patients with digestive symptoms alone were no different from chronic bronchitis with respect to reflux. The mechanism whereby reflux triggers pulmonary problems was investigated using the following 2 tests: scintiscan for pulmonary aspiration, and esophageal acid infusion (0.1N HCI). Six pulmonary aspirations were detected. Only asthmatics, with or without reflux, showed any significant variations in maximal expiratory flow at 50% and 25% of VC after HCI infusion. Thus, our results show that asthmatics differ from bronchitis patients by the characteristics of their reflux.

[Tolerance test to an inspiratory resistive load and resistive training of respiratory muscles. Preliminary critical study in kyphoscoliotic patients]. / Test de tolérance à une charge résistive inspiratoire et entraînement résistif des muscles respiratoires. Etude critique préliminaire chez 5 sujets cyphoscoliotiques.

Is increased tolerance to an additional inspiratory load after resistive training always due to respiratory muscle endurance? To answer this question, 5 kyphoscoliotic subjects were subjected to ventilation through a Y-shaped tube 3.2 cm in diameter during 10 minutes three times a day for 3 months. The subjects were divided into 3 groups. Group 1 (n = 3) trained with a non-linear resistance placed in the inspiratory branch of the tube during the first and third months and without additional load during the second month. Group 2 (n = 2) trained without inspiratory resistance during the first and third months and with an additional load during the second month. The load selected for the initial tolerance test (R1) was an inspiratory orifice with a diameter 0.5 mm wider than that of the orifice not tolerated during 3 min (R2). In each subject, ventilatory mode and time of tolerance on R1 were determined. This time was 10.8 +/- 6.8 min for the whole group. The tolerance test was repeated after each month of resistive or placebo training on R1 and R2. By grouping together the results of tolerance tests at 2 months after placebo training (4 measurements) and after resistive training (5 measurements), we found that the gain in endurance was similar without concomitant changes in volumes, air flows, VO2 max and time of endurance at 70% of VO2 max.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastroesophageal reflux in patients with asthma and chronic bronchitis.

To determine the relationship between gastroesophageal (GE) reflux and pulmonary disease, we studied 21 asthmatics, 30 chronic bronchitics, 6 patients with GE reflux and no pulmonary symptoms, and 10 control subjects; GE reflux was diagnosed by pH monitoring and GE scintiscanning. Frequency of GE reflux in the asthmatics was 57%; in the chronic bronchitics it was 56%. Pulmonary function tests did not show any differences between patients with or without reflux. The GE reflux episodes were more numerous but shorter in asthmatics than in chronic bronchitics. Patients with digestive symptoms alone were no different from chronic bronchitics with respect to reflux. The mechanism whereby reflux triggers pulmonary problems was investigated using the following 2 tests: scintiscan for pulmonary aspiration, and esophageal acid infusion (0.1N HCl). Six pulmonary aspirations were detected. Only asthmatics, with or without reflux, showed any significant variations in maximal expiratory flow at 50% and 25% of VC after HCl infusion. Thus, our results show that asthmatics differ from chronic bronchitics by the characteristics of their reflux.

[Characteristics and evolutive data of chronic respiratory diseases after respiratory intensive care. Evaluation of the Pneumology Department of the Pavillon Saint-François in Strasbourg between 1980 and 1985]. / Caractéristiques et données évolutives des affections respiratoires chroniques après réanimation respiratoire. (Bilan du service de pneumologie du Pavillon Saint-François de Strasbourg entre 1980 et 1985).

Between 1980 and 1985, 66 patients with chronic obstructive lung disease (respiratory deficit of the restrictive type) were admitted to our department after an episode of acute respiratory failure treated with assisted ventilation in an intensive care unit. These patients were in a particularly poor clinical condition, due to their previous long stay in the intensive care unit (mean 43 days), the high percentage of tracheotomies (mean 44%), the loss of autonomy of movement in 30% of the cases and the presence of an associated pathology in 45% of the patients. These data explain the high mortality observed in this group: 40% of the patients died within one year of the acute respiratory failure episode. Other prognostic factors, notably the patients' nutritional status, must also be taken into account.

[Pulmonary tuberculosis and cutaneous anergy to tuberculin]. / Tuberculose pulmonaire et anergie cutanée à la tuberculine.

A negative tuberculin test in a bacilliferous subject is an apparently paradoxical situation, since the first penetration of tubercle bacilli into the human body is known to induce hypersensitivity to tuberculin and to enhance cellular immunity. These two facets of cutaneous reaction are most probably related to lymphocyte populations of two different phenotypes. The authors found that 21% of skin tests were negative in patients carrying tubercle bacilli, with a higher frequency in elderly people and in subjects with low serum albumin levels and/or biochemical hepatic alterations. Helped by the literature, they are wondering about the significance and possible mechanisms of this situation.

[Idiopathic progressive pleuropulmonary fibrosis. Apropos of 2 cases]. / Fibroses pleuro-pulmonaires progressives idiopathiques. A propos de 2 observations.

The authors report two cases of retractile pleuroparenchymatous disease of the upper lobes of non known aetiology. They compare their results with those reported earlier by Stradling (20), Scadding (18), Davies (10) and attempt to identify the specific characteristics of the disease: progressive weight, loss frequent haemoptysis, apical onset, most often unilateral, with pleural involvement and progressive spread of the lesions which nevertheless remain predominantly in the upper lobes and are asymmetrical. The similarity with pulmonary fibrosis which occurs in ankylosing spondylitis is remarkable.