Pulmonary perspective: immunology in diagnosis and treatment of lung cancer.

The combination of the limits encountered with current therapies and the increased knowledge of immunology have opened perspectives for the use of immunomodulators in the management of lung cancer patients. Both humoral and cellular immunity are now evaluated in diagnosis and treatment of cancer. Monoclonal antibodies (MoAbs) against tumour-associated antigens are now tested with various imaging techniques to improve detection and staging of lung cancer. MoAbs are also used in therapeutic clinical trials as: 1) mediators of immune effector function; 2) carriers of cytotoxic agents; 3) agents to block tumour growth factor; or 4) anti-idiotype vaccines. Immune effector cells, such as natural killer (NK) cells, T- and B-lymphocytes, macrophages, dendritic cells and neutrophils, are present either within or around tumours and are likely to play a role in cancer. These cells, either alone or with cytokines, could provide new efficient therapeutic approaches, particularly if immunosuppression is involved in tumour progression. In this context, most recent studies using immune cells and molecular bioengineering, could provide additional antitumoral effects. Finally, the discovery of several tumour rejection antigens has revived the dream of designing tumour vaccines and active specific immunotherapy.

[Spontaneous pneumothorax. Results of pleural talc therapy using thoracoscopy]. / Pneumothorax spontané. Résultats du talcage pleural sous thoracoscopie.

The aim of this retrospective study is to evaluate the advantage of thoracoscopy and the efficacy of talcage in the treatment of spontaneous pneumothorax (SP). Two hundred cases have been analyzed with a follow-up of 1 to 8 years after the occurrence of the disorder. The ratio man/woman is 4/1. One hundred and forty two pneumothorax are considered as being of idiopathic origin and 58 are associated to bronchopneumopathy, with a mean age of 33 and 56 years, respectively. The percentage of smokers is 69.5% with a mean smoking of 14 packets/years. The endoscopic aspect of pleura is either normal (30%) or shows adhesions (23.5%), blebs (17%) or bullaes (29.5%). Thoracoscopy allowed talc poudrage in 191 patients and allowed to indicate the need for surgery in nine patients. The immediate success rate of talcage is 93.7%. In the group of immediate failure (6.3%), unexpected bullous structures (8/12) are found at tomodensitometry (TDM), as well as during surgery. Late recurrence is reported in 2 cases (1%) at 20 and 25 months. Radiological sequelaes are minimum (9%). Lung function testing in patients with idiopathic pneumothorax (n = 64) shows, before talc poudrage, signs of pulmonary hyperdistension (total lung capacity (TLC) at 116% of predicted values), reflecting the illness pathology, 3 months after talcage a discrete restrictive syndrome (TLC 93%) and one year after the partial recovery of the lost volume (TLC 105%). Tomodensitometry revealed to be complementary to thoracoscopy in secondary SP and very instructive in idiopathic SP after immediate failure of talc poudrage.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary immune cells in health and disease: polymorphonuclear neutrophils.

The pulmonary vasculature represents the largest reservoir of polymorphonuclear neutrophils (PMNs) in the human body. This is in striking contrast with the paucity of PMNs present in the normal airways and alveoli. However, the respiratory tract constitutes an easy access for microorganisms and particles present in inhaled air and, therefore, efficacious defence mechanisms are required. When the mucociliary clearance and the alveolar macrophages are over-whelmed, the rapid recruitment of PMNs from the lung vasculature appears to be a crucial response of the host against the pathogens. The regulation of adherence of PMNs to endothelial cells (EC), followed by the transendothelial migration are now better understood, and are under the control of a series of adhesion molecules modulated by bacterial and inflammatory mediators. In addition to their defensive role, PMNs have also been implicated in acute and chronic injurious diseases of the lung. Clearly, PMNs contain enough cytotoxic and proteolytic material to induce lesional changes. However, the release of this material is likely to be dependent on environmental factors, including mediators derived from other inflammatory and immune cells. The presence or absence of these factors could explain the fact that high numbers of PMNs can be observed in the airways and alveoli without major lesions whilst in other conditions, a marginal increase of PMNs in the respiratory tract can be associated with major damage and irreversible architectural changes in the lung.

Thoracoscopy in the diagnosis and management of chronic pleural effusions.

Thoracoscopy was performed in 76 patients with chronic pleural effusions in which thoracocentesis and blind needle biopsy failed to reach a precise diagnosis. Analysis of thoracoscopic biopsies provided a definitive diagnosis in 53 of the 76 subjects. The diagnoses included 35 malignant diseases in which the macroscopic appearance was diagnostic in only 27 patients. Among these 76 patients, a talc dusting was performed in the management of recurrent effusion in 33 patients. No recurrence of pleural effusion was observed after 1 month in 87% and after 6 months in 76% of patients with recurrent pleural effusion. We confirm that thoracoscopy is a safe and useful technique for the diagnosis of pleural effusion which substantially decreases the necessity for diagnostic thoracotomy and that talc dusting is effective to achieve pleurodesis.

Clara cell protein in serum and bronchoalveolar lavage.

The 10 kDa Clara cell protein was measured in serum and bronchoalveolar lavage (BAL) from 39 healthy subjects (14 smokers, 25 nonsmokers) and from 41 patients with respiratory disease (chronic obstructive pulmonary disease (COPD), sarcoidosis, lung cancer). Clara cell protein appears as one of the most abundant respiratory tract derived proteins, with values averaging 7% of the total protein content of lung lavages from healthy nonsmokers. A significant reduction of Clara cell protein was found in BAL from smokers and patients with COPD or lung cancer. The same pattern of change was found in the concentrations of Clara cell protein in serum. Pulmonary sarcoidosis did not affect absolute values of Clara cell protein in lung lavages but was associated with elevated levels in serum. Changes in lung lavage Clara cell protein differed from that of albumin, beta 2-microglobulin or the secretory component, since the latter were unaffected by smoking or COPD but increased in sarcoidosis and lung cancer. These results indicate that Clara cell protein in BAL or serum might serve as a sensitive indicator of nonciliated bronchial cell dysfunction.

Thoracoscopic lung biopsy in interstitial lung disease.

Thoracoscopic lung biopsy has been proposed as an alternative to open lung biopsy for the diagnosis of interstitial lung disease. We performed thoracoscopic lung biopsy under local anesthesia and diathermic coagulation in 33 non-immunocompromised patients with interstitial lung disease. A diagnosis was obtained in all patients. No severe complication was observed. The average time of drainage was 4 days. We confirm that this technique has advantages compared to open lung biopsy.

Local increase of antiprotease and neutrophil elastase-alpha 1-proteinase inhibitor complexes in lung cancer.

Tumour progression is dependent on many factors including antiproteases and proteases released by tumour cells or host cells infiltrating the tumour. In the present study, we evaluated the antiprotease content, namely alpha 2-macroglobulin (A2M) and alpha 1-proteinase inhibitor (A1PI) and neutrophil (PMN) elastase complexed with A1PI, in limited and extended lung cancer patients compared to a nonsmoker and smoker control population. Data showed that A2M and A1PI were increased in the involved lung from limited cancer when compared to normals. In extended lung cancer, A2M content was also increased in the uninvolved side. The concentration of PMN elastase-A1PI complex was increased on both sides in lung cancer patients (10.2 ng.ml-1 in the uninvolved side, 8.2 ng.ml-1 in the involved side) when compared to nonsmokers (1.9 ng.ml-1, p less than 0.001) and smokers (3.8 ng.ml-1, p less than 0.005). This increase was not solely due to the smoking habit. We conclude that antiproteases and PMN elastase complexed with antiprotease are increased in lung cancer area. This increase could result in extracellular changes in lung cancer.

Dental technician's pneumoconiosis. A report of two cases.

Diagnosis of pneumoconiosis was made in 2 dental technicians presenting with interstitial lung disease. The occupational origin of inhaled dust was confirmed by mineralogic analyses, which disclosed mainly large amounts of chromium-cobalt-molybdenum particles originating from Vitallium prostheses, but also showed abrasives (silica and silicon carbide) and asbestos in 1 patient. The presence of Vitallium and its chemical stability in bronchoalveolar lavage and lung several years after cessation of exposure confirm the resistance of this alloy to corrosion by body fluids. This contrasts with the high solubility of cobalt described in cobalt or hard metal disease. We suggest that dental technician's pneumoconiosis is a complex pneumoconiosis distinct from silicosis, asbestosis, or hard metal disease and that Cr-Co-Mo alloys play a role in its pathogenesis.

Alpha-2-macroglobulin, monomeric and polymeric immunoglobulin A, and immunoglobulin M in bronchoalveolar lavage.

The concentrations of alpha 2-macroglobulin (alpha 2M), IgM, and the various molecular forms of IgA were measured in unconcentrated bronchoalveolar lavage (BAL) of normal subjects and in that of patients with interstitial lung disease. In BAL of control subjects, as previously observed in other external secretions, orosomucoid-coefficient of excretion relative to albumin (RCE) = 1.1 (albumin RCE = 1)-IgG (RCE = 0.7 in nonsmokers), and alpha 2M (RCE = 0.04) appeared to be secreted mainly by seepage from plasma according to molecular size. The secretion of p-IgA (RCE = 22), IgM (RCE = 0.09), and transferrin (RCE = 1.2) was selective, suggesting either local lung synthesis of these components or their active transepithelial transport. Concentrations of p-IgA, alpha 2M, and IgM in BAL displayed RCE at least 10 times lower than in other external secretions, reflecting the unsignificant local synthesis of these components in alveolar septa. In interstitial lung diseases, including sarcoidosis, hypersensitivity pneumonitis, and other lung fibroses, all protein concentrations in BAL were raised. Increased seepage of plasma proteins across the blood-gas barrier accounted for the elevation of orosomucoid and p-IgA (RCE unchanged). It probably accounted for the appearance in BAL of a characteristic peak of serum type dimeric IgA unbound to secretory component (SC), for the reduced percentage of free SC (5% versus 27% in control subjects), and for part of the increased percentage of m-IgA (52% versus 28% in control subjects). Contribution of local synthesis, presumably by cells infiltrating the alveolar tissue, was indirectly demonstrated for m-IgA and IgG, which were selectively secreted, more than 2-fold greater than albumin.(ABSTRACT TRUNCATED AT 250 WORDS)