Tobacco smoking induces an inflammatory response in the lungs of all smokers but, for reasons that are still poorly understood, only a proportion of them develop chronic obstructive pulmonary disease (COPD). Recent evidence indicates that this inflammatory response persists after smoking cessation, suggesting some type of auto-perpetuation mechanism similar to that described in autoimmune disorders. T-lymphocytes (CD4+ and CD8+) have been implicated in the pathogenesis of both COPD and several autoimmune processes. A subtype of regulatory CD4+ T-cells expressing CD25 (Tregs) plays a critical role in the maintenance of peripheral tolerance and the prevention of autoimmunity, but their potential role in COPD has not been explored. The present study sought to evaluate maturation (CD45RA/CD45R0) and activation markers (CD28) of T-lymphocytes and to explore potential Treg abnormalities in COPD.Flow cytometry was used to characterise T-lymphocytes obtained from blood and bronchoalveolar lavage fluid (BALF) in 23 patients with moderate COPD, 29 smokers with normal lung function and seven never-smokers.The main findings were that in BALF: patients with COPD showed higher CD8+CD45RA+ and lower CD8+CD45R0+ than smokers with normal lung function; and compared with never-smokers, smokers with preserved lung function showed a prominent upregulation of Tregs that was absent in patients with COPD.These observations indicate a final maturation-activation state of CD8+ T-lymphocytes in chronic obstructive pulmonary disease and, for the first time, identify a blunted regulatory T-cell response to tobacco smoking in these patients, further supporting a potential involvement of the acquired immune response in the pathogenesis of the disease.

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Chronic obstructive pulmonary disease (COPD) is characterised by an excessive inflammatory response to inhaled particles, mostly tobacco smoking. Although inflammation is present in all smokers, only a percentage of them develop COPD. T-lymphocytes are important effector and regulatory cells that participate actively in the inflammatory response of COPD. They comprise the T-cell receptor (TCR)-ab (CD4+ and CD8+) and TCR-cd T-lymphocytes. The latter represent a small percentage of the total T-cell population, but play a key role in tissue repair and mucosal homeostasis.To investigate TCR-ab (CD4+ and CD8+) and TCR-cd T-lymphocytes in COPD, the present authors determined, by flow cytometry, the distribution of both subpopulations in peripheral blood and bronchoalveolar lavage (BAL) samples obtained from patients with COPD, smokers with normal lung function and never-smokers.The present study found that: 1) the distribution of CD4+ and CD8+ lymphocytes in blood and BAL was similar in all three groups; 2) compared with nonsmokers, cd T-lymphocytes were significantly increased in smokers with preserved lung function; and 3) this response was blunted in patients with COPD.These results highlight a novel, potentially relevant, pathogenic mechanism in chronic obstructive pulmonary disease.

A freebase cocaine-smoking woman developed relapsing fever, bronchoconstriction, arthralgias and weight loss. Pulmonary infiltrates, arthritis, microhaematuria, pruriginous skin rash and mononeuritis multiplex were later added to the clinical picture. Both skin and muscle biopsies showed eosinophilic angiitis. Improvement or worsening of her clinical picture repeatedly coincided with avoidance or use of smoked cocaine, respectively.We suggest that Churg-Strauss vasculitis may be a complication of smoking freebase cocaine. Eur Respir J., 1996, 9, 175-177 Various lung diseases related to the use of freebase cocaine have been reported [1,2]. Pulmonary infiltration with eosinophilia is an uncommon presentation of cocaine smoking [3][4][5][6]. We report a case of Churg-Strauss vasculitis in a patient whose clinical symptoms were clearly related to cocaine smoking. To our knowledge, this effect of cocaine abuse has not been described previously. Case reportA 39 year old woman had been a 40 cigarette·day -1 smoker since the age of 16 yrs. She had been using cocaine for the last 14 yrs and denied other toxic exposures and i.v. drug abuse. Her initial cocaine use had been limited to intranasal administration. Since then, she had occasionally suffered from wheezing which remitted with the inhalation of adrenergic β 2 -agonists. She had begun to use freebase "smoked" cocaine 8 months earlier. Shortly afterwards, she presented with dyspnoea on effort, wheezing, 20 kg weight loss and polyarthralgias. The patient was admitted because of sweats, 38˚C fever, dry cough and right pleuritic pain of 1 week's duration.Physical examination showed right inspiratory crackles and diffuse expiratory wheezes. Nasal examination was normal. Chest radiography disclosed an alveolar infiltrate in the right lower lobe. Electrocardiography (ECG) revealed tachycardia at 110 beats·min -1 with diffuse repolarization changes. Pulmonary function testing showed a forced vital capacity (FVC) of 2.6 L (79% of predicted) forced expiratory volume in one second (FEV1) 2.0 L (70% pred) and FEV1/FVC 77%. Arterial blood gas measurements performed with the patient breathing room air were: pH 7.42; arterial carbon dioxide tension (Pa,CO 2 ) 5.6 kPa (42 mmHg) and arterial oxygen tension (Pa,O 2 ) 6.9 kPa (52 mmHg). Leucocyte count was 11.9×10 9 cells·L -1 with 3% eosinophils, and serum immunoglobulin E (IgE) was 346 IU·mL -1 . Erythrocyte sedimentation rate (ESR) was 99 mm·h -1 . All bacteriological studies were negative. Testing for human immunodeficiency virus was also negative.The patient stopped smoking cocaine and was treated with bronchodilators and antibiotics. Marked clinical and radiological improvement was observed within a few days and the patient was discharged. Temporal relationship between cocaine exposure and laboratory data is shown in figure 1.Six months later, the patient began to smoke cocaine again and presented with three episodes of fever, cough, wheezing, arthralgias and peripheral lung infiltrates ( fig. 2),

In COPD, it is true that the small airways' wall shows a clear inflammatory pattern, with a high mononuclear infiltration and tissue remodeling. However, parenchymal interstitium shows a milder CD8(+) infiltration which, moreover, is not spatially related to emphysematous destroyed areas.