[Clinical study of interstitial lung disease in mixed connective tissue disease]. / Etude des pneumopathies interstitielles diffuses de la connectivite mixte.

Mixed connective tissue disease (MCTD) is characterized by a combination of clinical features of progressive systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, polymyositis/dermatomyositis, with a high anti-snRNP antibody titer. Respiratory manifestations, such as interstitial lung disease (ILD), are not well-described. Thirteen patients who met the diagnostic criteria for MCTD and showed ILD on high-resolution CT were analysed retrospectively. A restrictive pattern was found in 73% of cases and TLCO abnormalities in 90%. Exercise hypoxemia was observed in nine out of ten cases. The CT-scan pattern was compatible with non-specific interstitial pneumonia in seven cases and with usual interstitial pneumonia in five. Bronchoalveolar lavage showed lymphocytic alveolitis in two patients, neutrophil alveolitis in eight. Fifty percent ILD patients respond to steroids and immunosuppressive drugs. Progressive ILD (six in 13; 46%) compared with non-progressive ILD associated more systemic sclerosis manifestations (p<0.05). Progressive ILD tend to have more frequent pulmonary hypertension, neutrophilic alveolitis and honey combing pattern. MCTD-ILD characteristics are not specific. When systemic sclerosis manifestations are present, MCTD-ILD seems to associate more frequently pulmonary hypertension and progressive ILD.

Contribution of 92 kDa gelatinase/type IV collagenase in bronchial inflammation during status asthmaticus.

In order to assess inflammatory features related to severe asthma as compared with mild asthma, we investigated the secretion of 92 kDa gelatinase matrix metalloproteinase (MMP-9) in bronchial lavages of six patients undergoing mechanical ventilation (MV) for status asthmaticus (SA) and in six patients with mild asthma. Ten healthy nonventilated patients and four patients under MV without preexisting respiratory disease were also investigated. Patients with SA were characterized by prominent neutrophilic inflammation (82 +/- 4% versus 10% in mild asthma). On the basis of enzymatic and immunological analysis, results showed an acute 10- to 160-fold increase of 92 kDa gelatinase (MMP-9) concentration in epithelial lining fluid (ELF) from patients with SA, together with activated forms (46 and 26 kDa) of stromelysin-1 matrix metalloproteinase (MMP-3) and detectable concentration of free metallogelatinolytic activity (1-5 micrograms gelatin hydrolyzed/48 h/ml ELF). Concomitant elevated level of tissue inhibitor of metalloproteinase-1 (TIMP-1) was shown only in patients with SA, thus counterbalancing, at least partially, excess of activated 92 kDa gelatinase. Acutely enhanced albumin levels were only observed in patients with SA; in addition, 92 kDa gelatinase and albumin levels were significantly and positively correlated (r = 0.96, p < 0.0001), suggesting that 92 kDa gelatinase may account for increased bronchial permeability in patients with SA. Several arguments support that 92 kDa gelatinase during SA originates both from numerous activated chemoattracted neutrophils and from activated bronchial epithelial cells in response to in situ lung injury. The fact that no relevant change in ELF, albumin, MMP-9, MMP-3, TIMP-1, or laminin degradation products was observed during mild asthma, strongly supports that the mechanism of airway inflammation in SA is quite distinct from that observed in mild asthma.

[Acute silicosis. Clinical, radiologic, functional, and cytologic characteristics of the broncho-alveolar fluids. Observations of 6 cases]. / Silicose aiguë. Caractéristiques cliniques, radiologiques, fonctionnelles et cytologiques du liquide broncho-alvéolaire. A propos de 6 observations.

We describe six cases of acute silicosis which were characterised by an intense exposure to pure silica; there was a rapid onset with diffuse abnormalities on the radiological image and severe respiratory abnormalities. The duration of occupational exposure to silica was four to eighteen years. Three patients presented with a cough associated with disabling dyspnoea (stage III and IV). The physical examination showed finger clubbing in three patients and rales and crepitations on auscultation in two patients. There was general debility in four of the cases with weight loss. The chest x-ray showed a rapid progress with confluence of the diffuse nodular opacities. Respiratory function tests showed a restrictive ventilatory defect (mean +/- standard error of mean: TLC 67 +/- 5%, Vital Capacity +/- 7%, FEV1 63.5 +/- 6%) and alteration in the transfer factor for carbon monoxide (DLCO: 49.5 +/- 5%). The initial broncho-alveolar lavage showed a lymphocytosis (23.6 +/- 4.2%) associated with an alveolar neutrophilia (7 +/- 2.5%). A lung biopsy was carried out in three patients and a transbronchial biopsy in one patient confirming the diagnosis of silicosis in three cases and of silicoproteinosis in one case. After a period of eighteen months to 14 years, four patients died either due to cardiopulmonary complications of their disease (two cases) or to intercurrent disorders (two cases). The last two patients are currently stable.

[Management of hemoptysis in invasive pulmonary aspergillosis]. / Prise en charge des hémoptysies au cours de l'aspergillose pulmonaire invasive.

Invasive pulmonary aspergillosis is an opportunistic infection occurring in a background of severe immune depression. The majority of cases occur in patients who have malignant hematologic disease, particularly during chemotherapy induction or consolidations phases for acute non-lymphocytic leukemia. The principal risk factors are profound (PN < 500 per mm3) and prolonged (very high risk beyond 20 days) neutropenia, perturbed phagocyte function and cellular immune deficiency (AIDS, immunosuppressive treatment in organ and bone marrow recipients). Clinically, invasive pulmonary aspergillosis presents as acute non-specific pneumonia with cough, chest pain and fever. The severe infection rapidly becomes life-threatening. The development of massive hemoptysis is a major risk. We report four cases of invasive pulmonary aspergillosis in patients who had hemoptysis. All four patients developed non-specific pneumonia resistant to broad-spectrum antibiotics during post-chemotherapy aplasia. Computed tomography of the thorax and bronchoscopy with bronchoalveolar lavage was performed due to the occurrence of hemoptysis. In the first two cases, the patients were recovering from aplasia. The thoracic CT scan showed evidence of a cavitating mass with peripheral vessels. Bronchoscopy findings suggested mucosal lesions. The patients were managed surgically. Pathology confirmed the diagnosis of invasive pulmonary aspergillosis with the presence of ischemic necrosis of the pulmonary parenchyma harboring numerous aspergillus filaments. Outcome was favorable and chemotherapy was re-initiated in one case. These two patient died from their hematological disease a few months later. The other two patients remained in aplasia. A CT of the thorax showed multifocal infiltration with vascular contact. Bronchoscopy was again suggestive. One patient developed massive hemoptysis with respiratory distress. Embolization was performed but the patient died two days after onset of hemoptysis. In the last case, embolization was successful and outcome was favorable enabling a bone marrow allograft; the patient died a few months later from the hematological disease. The potential gravity of hemoptysis in the course of invasive pulmonary aspergillosis should lead to early treatment with emergency CT scan and, if possible, bronchoscopy with bronchoalveolar lavage to establish the therapeutic strategy based on surgical excision or embolization of the pulmonary or bronchial arteries.

[Initial manifestations and late diagnosis in chronic atrophic polychondritis: apropos of a series of 15 patients]. / Manifestations révélatrices et retard diagnostique dans la polychondrite chronique atrophiante: à propos d'une série de 15 malades.

An auricular or nasal chondritis or a saddle nose deformity are the initial manifestation in half of cases of relapsing polychondritis; the other initial manifestations are various and less evocative; polyarthritis, laryngo-tracheal symptoms, episcleritis which delay the diagnosis. From 15 cases of relapsing polychondritis, the diagnosis time from the first symptom are studied; this one is long, about 3 years and 6 months (from 3 months to 17 years) in 13/15 of the cases even if the first manifestation is typical (external chondritis). In two cases only, the diagnosis was established after the first attack. This late of diagnosis had socioeconomical impact and exposed to severe complications like tracheal chondritis.

Immunoreactivity for interleukin 3 and 5 and granulocyte/macrophage colony-stimulating factor of intestinal mucosa in bronchial asthma.

T lymphocytes and eosinophils are important components of the inflammatory cell infiltrate in bronchial mucosa in asthma. Because activated lymphocytes migrate through the thoracic duct and the general circulation to remote glandular and mucosal sites, we initiated this study to evaluate pathological abnormalities and immunoreactivity for interleukin (IL) 3, IL-5, and granulocyte/macrophage colony-stimulating factor (GM-CSF) of intestinal mucosa in bronchial asthma. 15 asthmatic patients, 8 nonasthmatic patients with chronic obstructive pulmonary disease, 6 atopic nonasthmatic healthy controls, and 6 nonatopic healthy controls were studied. Duodenal biopsies were performed by endoscopy. A significantly increased number of intraepithelial lymphocytes and eosinophils and a significant accumulation of mononuclear cells (lymphocytes and mast cells) and eosinophils in the lamina propria were detected in asthmatics and atopic controls. Immunostaining with antibodies directed against IL-3, IL-5, and GM-CSF was positive in asthmatics and atopic controls, whereas no staining was observed in nonatopic controls and chronic obstructive pulmonary disease. Combined ultrastructural study and immunogold labeling demonstrated that IL-3, IL-5, and GM-CSF were localized in eosinophils and mast cells. Although devoid of gastrointestinal symptoms, asthmatics and asymptomatic atopics had duodenal pathological abnormalities mimicking those observed in the bronchial mucosa in asthma, suggesting that the whole mucosal immune system is involved in bronchial asthma.