Frequent exacerbators--a distinct phenotype of severe asthma.

BACKGROUND: Exacerbations represent a major source of morbidity and mortality in asthma and are a prominent feature of poorly controlled, difficult-to-treat disease. OBJECTIVE: The goal of our study was to provide a detailed characterization of the frequent exacerbator phenotype and to identify risk factors associated with frequent and seasonal exacerbations. METHODS: Ninety-three severe asthmatics (SA) and 76 mild-to-moderate patients (MA) were screened and prospectively followed up for 1 year (NCT00555607). Medical history, baseline clinical data and biomarkers were used to assess risk factors for frequent exacerbations. RESULTS: During the study, 104 exacerbations were recorded in the SA group and 18 in the MA. Frequent exacerbators were characterized by use of higher doses of inhaled (1700 vs. 800 µg) and oral (6.7 vs. 1.7 mg) glucocorticosteroids, worse asthma control (ACQ score 2.3 vs. 1.4), lower quality of life (SGRQ score 48.5 vs. 33.3), higher sputum eosinophils (25.7% vs. 8.2%) and a more rapid decline in FEV1 /FVC ratio (-0.07 vs. -0.01 ΔFEV1 /FVC, frequent vs. non-frequent, respectively, P < 0.05). Exhaled NO > 45 p.p.b. and a history of smoking were associated with an increased risk of frequent exacerbations (odds ratios: 4.32 and 2.90 respectively). CONCLUSION AND CLINICAL RELEVANCE: We were able to distinguish and characterize a subphenotype of asthma subjects--frequent exacerbators--who are significantly more prone to exacerbations. Patients with FeNO > 45 p.p.b. and a history of smoking are at increased risk of frequent exacerbations and require careful monitoring in clinical practice.

EAACI position statement on asthma exacerbations and severe asthma.

Asthma exacerbations and severe asthma are linked with high morbidity, significant mortality and high treatment costs. Recurrent asthma exacerbations cause a decline in lung function and, in childhood, are linked to development of persistent asthma. This position paper, from the European Academy of Allergy and Clinical Immunology, highlights the shortcomings of current treatment guidelines for patients suffering from frequent asthma exacerbations and those with difficult-to-treat asthma and severe treatment-resistant asthma. It reviews current evidence that supports a call for increased awareness of (i) the seriousness of asthma exacerbations and (ii) the need for novel treatment strategies in specific forms of severe treatment-resistant asthma. There is strong evidence linking asthma exacerbations with viral airway infection and underlying deficiencies in innate immunity and evidence of a synergism between viral infection and allergic mechanisms in increasing risk of exacerbations. Nonadherence to prescribed medication has been identified as a common clinical problem amongst adults and children with difficult-to-control asthma. Appropriate diagnosis, assessment of adherence and other potentially modifiable factors (such as passive or active smoking, ongoing allergen exposure, psychosocial factors) have to be a priority in clinical assessment of all patients with difficult-to-control asthma. Further studies with improved designs and new diagnostic tools are needed to properly characterize (i) the pathophysiology and risk of asthma exacerbations, and (ii) the clinical and pathophysiological heterogeneity of severe asthma.

Safety and efficacy of a CXCR2 antagonist in patients with severe asthma and sputum neutrophils: a randomized, placebo-controlled clinical trial.

BACKGROUND: Increased numbers of neutrophils are reported in the airways of patients with severe asthma. It is not clear if they contribute to the lack of control and severity. There are currently no strategies to investigate this by decreasing neutrophil numbers in the airways. OBJECTIVE: To investigate the safety and efficacy of SCH527123, a selective CXCR2 receptor antagonist, in patients with severe asthma and increased number of neutrophils in sputum. METHODS: In a randomized, double-blind, parallel study, patients with severe asthma and sputum total cell count < 10 × 10(6) /g and neutrophils > 40% were randomized to SCH527123, 30 mg daily PO (n = 22) or placebo (n = 12) for 4 weeks. Primary end-points were safety and change in sputum and blood neutrophil counts. Secondary end-points were change in asthma control questionnaire (ACQ) score, minor and major exacerbations, spirometry and sputum neutrophil activation markers. RESULTS: The SCH 527123 caused a mean reduction of 36.3% in sputum neutrophil percentage compared to a 6.7% increase in the placebo arm (P = 0.03). The mean absolute neutrophil count in blood was reduced by 14% at the end of 4 weeks, but recovered by the 5th week. There were no differences in the overall rates of adverse events among the groups. There were fewer mild exacerbations (1.3 vs. 2.25, P = 0.05) and a trend towards improvement in the ACQ score (mean difference between groups of 0.42 points, P = 0.053). No statistically significant changes were observed in forced expiratory volume in 1 s (FEV (1)), sputum myeloperoxidase, IL8 or elastase. CONCLUSIONS: The SCH527123 is safe and reduces sputum neutrophils in patients with severe asthma. CLINICAL RELEVANCE: This new treatment provides an opportunity to investigate the role of neutrophils in severe asthma with potential clinical benefits. Larger studies of longer duration are needed to evaluate the impact on other outcomes of asthma including exacerbations.

Osteopontin expression and relation to disease severity in human asthma.

Recent studies have associated osteopontin (OPN) with allergic inflammation; however, its role in human asthma remains unclear. The aim of this study was to measure OPN levels in the serum, bronchoalveolar lavage fluid (BALF) and bronchial tissue of healthy controls and asthmatics, identify cellular sources of OPN and examine possible correlations between OPN expression, disease severity and airway remodelling. Serum samples were obtained from 35 mild-to-moderate asthmatics, 19 severe asthmatics and 17 healthy controls in the steady state and in cases of exacerbation. Of these subjects, 29 asthmatics and nine controls underwent bronchoscopy with endobronchial biopsy and BALF collection. OPN expression was determined by ELISA and immunohistochemistry/immunofluorescence. Reticular basement membrane thickness and goblet cell hyperplasia were also determined. Serum and BALF OPN levels were significantly increased in all asthmatics in the steady state, whereas serum levels decreased during exacerbations. OPN was upregulated in the bronchial tissue of all patients, and expressed by epithelial, airway and vascular smooth muscle cells, myofibroblasts, T-lymphocytes and mast cells. OPN expression correlated with reticular basement membrane thickness and was more prominent in subepithelial inflammatory cells in severe compared to mild-to-moderate asthma. OPN expression is upregulated in human asthma and associated with remodelling changes, and its subepithelial expression correlates with disease severity.

Messenger RNA expression of the cytokine gene cluster, interleukin 3 (IL-3), IL-4, IL-5, and granulocyte/macrophage colony-stimulating factor, in allergen-induced late-phase cutaneous reactions in atopic subjects.

Cryostat sections from skin biopsies from 24-h allergen-induced late-phase cutaneous reactions (LPR) in 14 human atopic subjects were hybridized with 35S-labeled RNA probes for a number of cytokines. mRNA was detected for interleukin 3 (IL-3) (8/14), IL-4 (10/14), IL-5 (11/14), and granulocyte/macrophage colony-stimulating factor (GM-CSF) (13/14). Only 5 of 14 gave hybridization signals for IL-2, and 0 of 14 for interferon gamma. Biopsies from diluent controls gave only occasional weak signals. These results suggest that cells infiltrating the site of the 24-h LPR transcribe mRNA for the IL-3, IL-4, IL-5, and GM-CSF gene cluster and support the hypothesis that atopy is associated with preferential activation of cells having a similar cytokine profile to the murine T helper type 2 subset.

IL-5 expression and release from human CD34 cells in vitro; ex vivo evidence from cases of asthma and Churg-Strauss syndrome.

BACKGROUND: Eosinophils develop from hematopoietic CD34(+) progenitor cells in the bone marrow (BM) under the influence of Interleukin-5 (IL-5). The primary source of IL-5 is T-lymphocytes, although other sources may exist. The aims of this study were to determine whether CD34(+) cells from human peripheral blood (PB) and BM have the capacity to produce IL-5 when stimulated in vitro, and secondly, whether an elevated number of IL-5-producing CD34(+) cells can be found in situ in ongoing eosinophilic disease. METHODS: CD34(+) cells from PB and BM were stimulated in vitro, and IL-5 production and release was assessed by ELISA, ELISPOT, flow cytometry and immunocytochemistry. Blood and BM from a patient with Churg-Strauss syndrome were analyzed by flow cytometry for CD34(+)/IL-5(+) cells, and immunohistochemical staining of CD34(+)/IL-5(+) cells in bronchial biopsies from an asthmatic patient was performed. RESULTS: Both PB and BM CD34(+) cells can produce and release IL-5 when stimulated in vitro. In the Churg-Strauss patient, IL-5-producing CD34(+) cells were found in PB and BM. Oral glucocorticoid treatment markedly decreased the number of IL-5-positive CD34 cells in the BM. CD34(+)/IL-5(+) cells were present in a patient with asthma. CONCLUSION: CD34(+) cells in blood and BM are capable of producing IL-5 both in vitro and in vivo in humans, arguing that these cells may have the capacity to contribute to eosinophilic inflammation. Consequently, targeting CD34(+) progenitor cells that produce and release IL-5 may be effective in reducing the mobilization of eosinophil lineage-committed cells in eosinophilic-driven diseases.

Modulation of the epithelial inflammatory response to rhinovirus in an atopic environment.

BACKGROUND: Immune responses to rhinovirus (RV) as well as direct effects of RV on respiratory epithelium may contribute to the induction of asthma exacerbations. OBJECTIVE: To evaluate the effect of the environment resulting from an atopic immune response on RV-induced epithelial inflammation, replication and cytotoxicity. METHODS: Peripheral blood mononuclear cells (PBMC) from atopic asthmatic subjects and matched controls (12 pairs) were isolated and stimulated by RVs. Human bronchial epithelial (BEAS-2B) cells were infected with RV in the presence of conditioned media from RV-stimulated PBMC cultures. IL-6, IL-8, RANTES and TGF-beta1 levels were measured by ELISA, RV-induced cytotoxicity by a colorimetric method and RV titres on Ohio-HeLa cells. RESULTS: RV-induced epithelial production of IL-6, IL-8 and RANTES was significantly lower, while TGF-beta1 was higher when cells were exposed to conditioned media from atopic asthmatic subjects compared with those from normal controls. Exposure to the 'atopic' environment also resulted in elevated RV titres and increased RV-induced cytotoxicity. CONCLUSIONS: Under the influence of an atopic environment, the epithelial inflammatory response to RV is down-regulated, associated with increased viral proliferation and augmented cell damage, while TGF is up-regulated. These changes may help explain the propensity of atopic asthmatic individuals to develop lower airway symptoms after respiratory infections and indicate a mechanism through which viral infections may promote airway remodelling.

Skin reactivity and local cell recruitment in human atopic and nonatopic subjects by CCL2/MCP-1 and CCL3/MIP-1alpha.

BACKGROUND: Monocyte chemotactic protein (MCP-1/CCL2), the ligand for CCR2 and CCR5, and macrophage inflammatory protein-1alpha (MIP-1alpha/CCL3), the ligand for CCR1 and CCR5, are potent chemo-attractants in vitro and produce lesions in experimental animals, which resemble immediate and delayed-type hypersensitivity (DTH) reactions. CCL3 induces mononuclear cell and granulocyte infiltration in human atopic and nonatopic skin. Whether CCL2 (MCP-1) has comparable activity in man is uncertain as is the capacity of both the chemokines to elicit immediate- and DTH-like reactions in humans. METHODS: Inflammatory cells were counted by immunohistochemistry in 24 and 48-h skin biopsies from atopics and nonatopics after intradermal injection of CCL2 and CCL3. Immediate (15 min) wheals-and-flares and delayed (24 and 48 h) indurations were also recorded. RESULTS: Both chemokines induced immediate- (15 min) and delayed (24 and 48 h) reactions, which were associated with significant infiltrations of CD68+ macrophages, CD3+, CD4+ (but not CD8+) T cells, neutrophils, and eosinophils in biopsies from injection sites. CCL2, but not CCL3, also induced infiltration of basophils. Neither chemokine produced significant changes in the numbers of tryptase+ cutaneous mast cells. There were no differences in the pattern of skin reactivity or the numbers of infiltrating leukocytes in response to CCL2 and CCL3 between atopic and nonatopic subjects. In general, maximal infiltration of inflammatory cells was observed at the 24-h, rather than the 48-h, time point. CONCLUSIONS: CCL2 and CCL3 induce both immediate and delayed skin reactions in atopics and nonatopics, and evoke a similar profile of local T cell/macrophage and granulocyte recruitment which, in general, confirm previous in vitro findings and in vivo experimental animal data.

Influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses.

We have studied the influence of grass pollen immunotherapy on cellular infiltration and cytokine mRNA expression during allergen-induced late-phase cutaneous responses. In a double-blind, placebo-controlled trial of immunotherapy in 40 adult hay fever sufferers, clinical improvement was accompanied by a decrease in the size of the late-phase skin response. When the immunotherapy-treated group was compared with the placebo group, analysis of skin biopsies obtained 24 h after intradermal allergen revealed a significant reduction in the number of infiltrating CD3+ (P = 0.04) and CD4+ (P = 0.009) cells and a trend for a decrease in EG2+ eosinophils (P = 0.08). Treatment did not influence allergen-induced recruitment of CD8+ cells, neutrophils, or macrophages. Unexpected increases in expression of CD25 (P = 0.006) and HLA-DR (P = 0.007) were observed in the actively treated group. In situ hybridization using a panel of riboprobes demonstrated "TH2-type" (IL-4, IL-5) cytokine mRNA responses in both groups of patients. In contrast, significant hybridization for IL-2 (8/16 patients, P = 0.02) and for interferon-gamma (6/16 patients, P = 0.04) was observed only in the actively treated group. These findings indicate that immunotherapy is associated with suppression of allergen-induced CD4+ T lymphocyte infiltration, but among the cells that are recruited, there is upregulation of CD25 and HLA-DR. At least in this model, immunotherapy does not appear to affect expression of TH2-pattern cytokines in response to allergen exposure, but expression of mRNA for Th1-type cytokines was enhanced in half of the patients. The results support the view that immunotherapy may possibly be working through induction of T cell tolerance.

Diagnostic usefulness of 5 tumor-markers in patients with primary lung-cancer.

Thymidine kinase (TK), carbohydrate antigen 19-9 (CA 19-9), carbohydrate antigen 125 (CA 125), squamous cell carcinoma antigen (SCC) and tissue polypeptide antigen (TPA), were evaluated in 104 untreated patients with primary lung cancer acid 55 patients with benign lung disease. The mean concentrations of TPA and CA 125 were significantly higher in lung cancer patients than in benign controls (p<0.001). The concentrations of all the tumor markers were well correlated with the stage of lung cancer. In respect to sensitivity, specificity and accuracy, TPA was superior to the other tumor markers tested (70.2%, 88.8% and 75.8% respectively). When TPA was combined with the other markers, sensitivity increased from 70.2% to 98%, but as the number of combined markers became larger, specificity decreased (from 88.8% to 40%). Nevertheless, the combination of TPA and CA 19-9 showed significantly higher sensitivity in patients with resectable non small eel lung cancer (NSCLC) and limited small cell lung cancer (SCLC) than TPA alone (87% vs 49% and 88.8% vs 44.4% respectively) without significant differences in specificity. The relative possibility of lung cancer was 15% when one tumor marker was positive. This possibility increased to 82%-100% when more than three markers were positive.

Unevenness of ventilation assessed by the expired CO(2) gas volume versus V(T) curve in asthmatic patients.

Recently, we have shown that the expired CO2 gas volume versus tidal volume (VCO2-VT) curve is a useful tool for assessing unevenness of ventilation because it allows the separation of tidal volume into three functional compartments: (a) the CO2-free expired air (V0), (b) the transitional volume (Vtr), (c) the alveolar volume (VA) and the measurement of alveolar FCO2 during resting breathing in normal subjects and patients with COPD. In this paper, we have investigated whether changes pertaining to unevenness of ventilation taking place immediately after the administration of methacholine can be assessed using the VCO2-VT curve in asthmatic patients. The VCO2-VT curve was obtained during tidal breathing from 16 stable asthmatic patients who underwent a methacholine challenge test. It has been found that the Vtr, and hence Bohr's dead space (VD,Bohr = V0 + Vtr), over tidal volume ratios were significantly increased immediately after the methacholine administration, whilst the V0 over tidal volume ratio was not affected. The change of the above ratios was not related to the percentage decrease of FEV1.0 following methacholine administration.

Recurrent respiratory papillomatosis with malignant transformation in a young adult.

The term 'papilloma' was first used by Mackenzie 100 years ago, who claimed that this was the most benign tumour of the larynx. Today papillomas are considered to be caused by the Human Papilloma Virus group (H.P.V.). The majority of patients suffering from this disease which is also referred to as 'recurrent respiratory papillomatosis' require multiple surgical operations for tumour removal. Malignant transformation of papillomas, which is a rare condition, is considered to occur mainly to irradiated patients. The following report describes the case of a male patient, with a history of vocal cord papillomas since his first year of age, who developed bronchial and pulmonary spread of the disease. He died at the age of 26 years because of squamous cell carcinoma which was related to the malignant transformation of the pulmonary papillomas.

Prevalence of asthma and asthma-like symptoms in Athens, Greece.

Asthma is a common chronic condition and there is evidence that its prevalence may be rising. The European Respiratory Health Survey (ECRHS) was planned to produce comparable data on asthma epidemiology in Europe. In Greece, in particular, a similar study has not been conducted previously and no epidemiological data are available on adult asthma prevalence. Furthermore, the role of air pollution in the pathogenesis of asthma is currently an issue of debate. Athens is a city with high air pollution, and a study of asthma epidemiology in this city may confirm or refute a possible link with the expression of asthma. A questionnaire developed by the ECRHS was sent to a random sample of 3533 households in Peristeri, an industrialized borough of Athens. Responses were received from 2774 households (response rate 78%). Of all the data on individual subjects, only those from 3325 adults aged 20-44 years were considered, according to the study protocol. The self-reported current prevalence of asthmatic attacks and asthma-like symptoms were as follows: asthma attack 2.4%, use of asthma medication 2.1%, awakening by shortness of breath 5.6%, awakening by cough 17.8%, wheezing 15.8% and nasal allergies 18.4%. It is concluded that the prevalence of asthma and related symptoms in this region of Athens is rather low, despite the high air-pollution levels in the city.

Tumour necrosis factor, interleukin-1 and adenosine deaminase in tuberculous pleural effusion.

Tumour necrosis factor (TNF) and interleukin-1 (IL-1) are powerful mediators with a key role in inflammation. This study was undertaken to study the presence of TNF and IL-1 in tuberculous effusion where there is marked inflammation and where examination of the pleural fluid may give information about the local inflammatory reaction. Adenosine deaminase activity (ADA, a marker of TB pleurisy) was also tested. Tumour necrosis factor, IL-1 and ADA levels were measured in the pleural fluid and serum of 97 patients; 33 with tuberculous effusion, 33 with malignant effusion, and 31 patients with benign non-tuberculous effusion. Pleural fluid TNF and ADA levels were higher in tuberculous (TB) patients than in patients with benign disorders or cancer (P < 0.01). Serum TNF levels were also higher in TB patients than other benign (P < 0.01) or malignant (P < 0.05) effusions. There was a positive correlation between serum and pleural fluid values (r = 0.998-0.999, P < 0.001) although pleural fluid concentration was higher (P < 0.001), possibly suggesting local production in the pleural cavity. Pleural fluid IL-1 levels were not raised in any patient group but there was a positive correlation between TNF and IL-1. In addition, a positive correlation was found between TNF and ADA levels, probably indicating some common production mechanism. Furthermore, ADA sensitivity in the diagnosis of tuberculous effusion was augmented by the combined use of TNF and ADA. The use of both these markers may prove useful in the differential diagnosis of TBC pleurisy.

A single-blind crossover study of two different slow release theophylline preparations.

In a single-blind crossover study, two slow release theophylline preparations were evaluated in 18 patients with chronic bronchitis or asthma without cardiac, renal or liver disease. After randomization into two groups, patients were treated, in a crossover study design, with 600 mg choline theophyllinate or 300 mg anhydrous theophylline administered orally every 12 h for 7 days. A 2-day washout period separated the two periods of treatment evaluation. Blood samples in which plasma theophylline concentration was to be measured were taken at 7.30 a.m., 2.00 p.m. and 7.30 p.m. during the last 5 days of therapy with each drug. The mean fluctuation in plasma theophylline concentration was less than or equal to 40% in all 18 patients taking choline theophyllinate yet in only 15 (83%) patients administered anhydrous theophylline. Salbutamol inhaler was more frequently required for the relief of bronchospasm when taking anhydrous theophylline than when taking choline theophyllinate (total of 41 vs 25 puffs, respectively, over 7 days). Drug-related adverse reactions occurred in four patients while taking anhydrous theophylline and in one patient while taking choline theophyllinate.

Usefulness of immunotherapy in patients with severe summer hay fever uncontrolled by antiallergic drugs.

OBJECTIVE: To evaluate the efficacy and safety of immunotherapy (hyposensitisation) in patients with severe summer hay fever. DESIGN: A randomised, double blind, placebo controlled study of a biologically standardised depot grass pollen extract. SETTING: Allergy clinic, Royal Brompton and National Heart Hospital, London. PATIENTS: 40 adults (mean age 35 years) with a history of severe grass pollen allergy uncontrolled by standard antiallergic drugs. Patients with perennial asthma were specifically excluded. INTERVENTION: Patients were randomised to receive either an active preparation (Alutard SQ, a grass pollen (Phleum pratense) extract) or placebo at a rate of two subcutaneous injections a week in increasing doses until a maintenance dose was reached. This maintenance dose was given once a month. MAIN OUTCOME MEASURES: Clinical efficacy was evaluated by symptom and drug diary cards, visual analogue scores during the grass pollen season, and a postseasonal assessment by the patients and a doctor. Conjunctival and skin sensitivity to local allergen provocation was measured before and after eight months of treatment. RESULTS: There was a highly significant decrease (median Alutard SQ v median placebo (95% confidence interval for difference between medians] in total symptom scores (p=0.001) in the Alutard SQ treated group (360 v 928 (238 to 825]. Significant differences were also found in total drug use (p=0.002, 129 v 627 (178 to 574]. Visual analogue symptom scores were also reduced in the active group (p=0.02, 2.2 v 5.5 (-4.8 to -0.5]. The postseasonal assessment, by either the doctor or the patients, showed a large improvement (p less than 0.001) in favour of Alutard SQ. Provocation tests showed a greater than 10-fold reduction for the active group in immediate conjunctival allergen sensitivity (p=0.001), a 40% decrease in early phase response (p=0.02), and a 57% decrease in the late phase (p=0.001) cutaneous response after intradermal allergen. A total of 523 active injections were given. There was one systemic reaction at 10 minutes after injection, which was rapidly reversed with intramuscular adrenaline. There was one mild delayed urticarial reaction at 2 1/2 hours. CONCLUSION: Immunotherapy is effective in patients with severe summer hay fever, but immediate anaphylactic reactions limit its use to specialised centres. Patient selection is extremely important, and chronic perennial asthma should be specifically excluded. As serious reactions occur within minutes a two hour wait for all patients after each injection seems unnecessary.

Multiple tuberculous abscesses and mediastinal lymphadenitis with no pulmonary involvement in an immunocompetent patient.

Tubercular cold abscesses secondary to neighbouring bone involvement are a well-known clinical manifestation of extra-pulmonary tuberculosis. However, primary soft tissue tuberculous abscesses with no pulmonary involvement in immuno-competent patients are very uncommon. A rare case of multiple primary intrathoracic and extraperitoneal soft tissue tuberculous abscesses and mediastinal lymph node tuberculosis with no pulmonary involvement is reported. This case demonstrates the need for a high index of suspicion for such rare presentations of extra-pulmonary tuberculosis in patients from endemic areas.

Differences in microsatellite DNA level between asthma and chronic obstructive pulmonary disease.

Previous studies have shown that microsatellite (MS) DNA instability (MSI) is detectable in sputum cells in chronic obstructive pulmonary disease (COPD) and asthma. The aim of the present study was to investigate whether asthma and COPD could be distinguished at the MS DNA level. DNA was extracted from sputum cells and white blood cells from 63 COPD patients, 60 non-COPD smokers, 36 asthmatics and 30 healthy nonsmokers. Ten MS markers located on chromosomes 2p, 5q, 6p, 10q, 13q, 14q and 17q were analysed. No MSI was detected in non-COPD smokers or healthy nonsmokers. A significantly higher proportion of COPD patients exhibited MSI (49.2%) compared to asthmatics (22.2%). MSI was detected even in the mild stages of COPD (33.3%) and asthma (22.2%). No relationship was found between MSI and COPD severity. The most frequently affected marker was D14S588 (17.5% in COPD and 2.7% in asthma). The markers D6S344, G29802 and D13S71 showed alterations only in COPD, and G29802 was associated with a significantly decreased forced expiratory volume in one second FEV1 (% predicted), whereas MSI in D6S344 was associated with a significantly higher FEV1 (% pred). The frequency of microsatellite instability was higher in chronic obstructive pulmonary disease than in asthma, and microsatellite instability in three workers showed chronic obstructive pulmonary disease specificity. However, further studies are needed to verify the differences between chronic obstructive pulmonary disease and asthma at the microsatellite level.