Study of correlation between forced vital capacity and demand for healthcare services in severe asthmatics.

BACKGROUND: Involvement of the small airways may be related to increased severity and increased demand for health care services and incurring in high costs, private or for the healthcare system. The hyperinflation consequent to this involvement reduces lung volumes, such as FVC, FEV1 and SVC. The aim of this study was to evaluate the correlation between the predicted values of FVC, FEV1 and SVC with the demand for healthcare services by severe asthmatics. METHODS: We retrospectively evaluated in order of arrival, the medical records of 98 patients with severe asthma, in step 4 treatment in the intercritical period of the disease, correlating the number of times each patient sought health care services represented by admissions to the ER, ICU and hospital wards due to asthma, in the year before the last spirometry and the predicted values of FVC, FEV1 and SVC. RESULTS: Our sample showed a clear and significant negative correlation between the predicted values of FVC, FEV1 and SVC and demand for healthcare services. CONCLUSION: For this sample we conclude, that reduced forced vital capacity correlated with asthma severity, defined by greater demand for care in the ER, ICU and hospital ward and was more evident in women.

The clinical and integrated management of COPD.

COPD is a chronic pathological condition of the respiratory system characterized by persistent and partially reversible airflow obstruction, to which variably contribute remodeling of bronchi (chronic bronchitis), bronchioles (small airway disease) and lung parenchyma (pulmonary emphysema). COPD can cause important systemic effects and be associated with complications and comorbidities. The diagnosis of COPD is based on the presence of respiratory symptoms and/or a history of exposure to risk factors, and the demonstration of airflow obstruction by spirometry. GARD of WHO has defined COPD "a preventable and treatable disease". The integration among general practitioner, chest physician as well as other specialists, whenever required, assures the best management of the COPD person, when specific targets to be achieved are well defined in a diagnostic and therapeutic route, previously designed and shared with appropriateness. The first-line pharmacologic treatment of COPD is represented by inhaled long-acting bronchodilators. In symptomatic patients, with pre-bronchodilator FEV1 < 60%predicted and ≥ 2 exacerbations/year, ICS may be added to LABA. The use of fixed-dose, single-inhaler combination may improve the adherence to treatment. Long term oxygen therapy (LTOT) is indicated in stable patients, at rest while receiving the best possible treatment, and exhibiting a PaO2 ≤ 55 mmHg (SO2<88%) or PaO2 values between 56 and 59 mmHg (SO2 < 89%) associated with pulmonary arterial hypertension, cor pulmonale, or edema of the lower limbs or hematocrit > 55%. Respiratory rehabilitation is addressed to patients with chronic respiratory disease in all stages of severity who report symptoms and limitation of their daily activity. It must be integrated in an individual patient tailored treatment as it improves dyspnea, exercise performance, and quality of life. Acute exacerbation of COPD is a sudden worsening of usual symptoms in a person with COPD, over and beyond normal daily variability that requires treatment modification. The pharmacologic therapy can be applied at home and includes the administration of drugs used during the stable phase by increasing the dose or modifying the route, and adding, whenever required, drugs as antibiotics or systemic corticosteroids. In case of patients who because of COPD severity and/or of exacerbations do not respond promptly to treatment at home hospital admission should be considered. Patients with "severe or "very severe COPD who experience exacerbations should be carried out in respiratory unit, based on the severity of acute respiratory failure. An integrated system is required in the community in order to ensure adequate treatments also outside acute care hospital settings and rehabilitation centers. This article is being simultaneusly published in Multidisciplinary Respiratory Medicine 2014; 9:25.

Candidate genes for COPD in two large data sets.

Lack of reproducibility of findings has been a criticism of genetic association studies on complex diseases, such as chronic obstructive pulmonary disease (COPD). We selected 257 polymorphisms of 16 genes with reported or potential relationships to COPD and genotyped these variants in a case-control study that included 953 COPD cases and 956 control subjects. We explored the association of these polymorphisms to three COPD phenotypes: a COPD binary phenotype and two quantitative traits (post-bronchodilator forced expiratory volume in 1 s (FEV1) % predicted and FEV1/forced vital capacity (FVC)). The polymorphisms significantly associated to these phenotypes in this first study were tested in a second, family-based study that included 635 pedigrees with 1,910 individuals. Significant associations to the binary COPD phenotype in both populations were seen for STAT1 (rs13010343) and NFKBIB/SIRT2 (rs2241704) (p<0.05). Single-nucleotide polymorphisms rs17467825 and rs1155563 of the GC gene were significantly associated with FEV1 % predicted and FEV1/FVC, respectively, in both populations (p<0.05). This study has replicated associations to COPD phenotypes in the STAT1, NFKBIB/SIRT2 and GC genes in two independent populations, the associations of the former two genes representing novel findings.

Standards of care and clinical predictors in patients hospitalised for a COPD exacerbation--the Italian SOS (Stratification Observational Study).

BACKGROUND AND AIMS: Hospitalisations for chronic obstructive pulmonary disease (COPD) exacerbations are major events in the natural history of the disease in terms of survival, quality of life and risk of further episodes of exacerbation. The aims of study were to evaluate: 1. adherence to recommended standards of care; and 2. clinical factors influencing major outcomes during hospitalisation for an episode of COPD exacerbation and within a 6-month follow-up. METHODS: An observational, prospective study was conducted in 68 centres. Assessment of standards of care included diagnostic procedures (such as pulmonary function tests and microbiology) and management options (such as drug therapies, vaccinations and rehabilitation). Outcome measures relevant to the hospitalisation were: survival, need for mechanical ventilation, and length of stay (LOS). Outcomes at 6-months were: survival, exacerbations and hospitalisations for an exacerbation. Multivariate logistic regression was applied to evaluate the relation between clinical factors and outcomes. RESULTS: 931 patients were enrolled. Only 556 patients (59.7%) were diagnosed COPD and stratified for severity with the support of spirometry (FEV1/VC < or = 0.7) and were considered for outcome analysis. Among treatments, pulmonary rehabilitation and anti-smoking counselling were applied infrequently (14.5 and 8.1% of patients, respectively). Within six months 63 COPD patients (17.7%) had at least one episode of exacerbation prompting a further hospitalisation and 19 died (5.3%). Predictor of mortality was the co-morbidity Charlson index (odds ratio, OR 10.3, p=0.03 CI: 1.25-84.96). A further hospitalisation was predicted by hospitalisation for an exacerbation in the previous 12 months (OR 3.59, p=0.003 CI: 1.54-8.39). CONCLUSIONS: Standards of care were far lower than recommended, in particular 40% of patients were labelled as COPD without spirometry. COPD patients with a second hospitalisation in 12 months for an exacerbation had about 3 times the risk of suffering a new episode and hospitalisation in the following six months.

GOLD severity stratification and risk of hospitalisation for COPD exacerbations.

BACKGROUND AND AIM: The Italian Costs for Exacerbations in COPD ("ICE") study, following a pharmacoeconomic assessment of costs due to COPD exacerbations (primary endpoint), aimed also at evaluating (secondary endpoint) which clinical factors, among those considered for cost-analysis, may, at follow up, present a risk of new exacerbations and re-admission to hospital. MATERIALS AND METHODS: A prospective, multicentre study was carried out on COPD patients admitted to 25 Hospital Centres as a result of an exacerbation from October-December 2002. Following discharge, a 6-month follow-up was performed in each patient via three bi-monthly telephone interviews with a questionnaire administered by an investigator clinician. RESULTS: 570 patients were eligible for data processing, mean age 70.6 years (+/- 9.5 standard deviation, SD), males 69.2%. According to GOLD, severity stratification was as follows: moderate 36.4%; severe 31.3%; very severe 32.3%. 282 patients experienced at least one exacerbation at follow up, 42% of exacerbations requiring hospitalisation. No significant association was seen between exacerbations and GOLD stage or co-morbidities or treatments except LTOT. Conversely, COPD functional severity influenced hospitalisations very significantly, with relative risks 2.6 (95% Confidence Interval, CI 1.8-3.8) and 2.0 (CI 1.3-2.8) (GOLD very severe versus moderate and severe, respectively), and 1.3 (CI 0.85-2.1) (GOLD severe versus moderate). Hospitalisations were also significantly associated with treatments denoting more severe conditions (oral corticosteroids, oral theophylline, and LTOT). CONCLUSIONS: Severity stratification of COPD patients according to respiratory function classes as outlined in GOLD guidelines and need for LTOT are confirmed as important predictors of hospitalisation for an exacerbation.

Costs of chronic obstructive pulmonary disease (COPD) in Italy: the SIRIO study (social impact of respiratory integrated outcomes).

Chronic respiratory diseases affect a large number of subjects in Italy and are characterized by high socio-health costs. The aim of the Social Impact of Respiratory Integrated Outcomes (SIRIO) study was to measure the health resources consumption and costs generated in 1 year by a population of patients with chronic obstructive pulmonary disease (COPD) in a real-life setting. This bottom-up, observational, prospective, multicentric study was based on the collection of demographic, clinical, diagnostic, therapeutic and outcome data from COPD patients who reported spontaneously to pneumological centers participating in the study, the corresponding economic outcomes being assessed at baseline and after a 1-year survey. A total of 748 COPD patients were enrolled, of whom 561 [408 m, mean age 70.3 years (SD 9.2)] were defined as eligible by the Steering Committee. At the baseline visit, the severity of COPD (graded according to GOLD 2001 guidelines) was 24.2% mild COPD, 53.7% moderate and 16.8% severe. In the 12 months prior to enrollment, 63.8% visited a general practitioner (GP); 76.8% also consulted a national health service (NHS) specialist; 22.3% utilized Emergency Care and 33% were admitted to hospital, with a total of 5703 work days lost. At the end of the 1-year survey, the severity of COPD changed as follows: 27.5% mild COPD, 47.4% moderate and 19.4% severe. Requirement of health services dropped significantly: 57.4% visited the GP; 58.3% consulted an NHS specialist; 12.5% used Emergency Care and 18.4% were hospitalized. Compared to baseline, the mean total cost per patient decreased by 21.7% (p<0.002). In conclusion, a significant reduction in the use of health resources and thus of COPD-related costs (both direct and indirect costs) was observed during the study, likely due to a more appropriate care and management of COPD patients.

Costs of asthma in Italy: results of the SIRIO (Social Impact of Respiratory Integrated Outcomes) study.

Bronchial asthma is a costly disease and the correlated social impact is ever increasing. The aim of the Social Impact of Respiratory Integrated Outcomes (SIRIO) study was to measure the health resources consumption and the costs generated in 1 year by asthmatic patients investigated in a real-life setting. This bottom-up, observational, prospective, multicentric study was based on the collection of demographic, clinical, diagnostic, therapeutic and outcome data of 577 patients with bronchial asthma who reported spontaneously to the pneumology centers involved in the study. Of these, 485 patients (300 f, mean age 49.2 years+/-16.3 S.D.) were eligible for analysis. At the baseline visit, the asthma severity was as follows: 26.2% intermittent, 37.1% mild persistent, 29.5% moderate, and 6.6% severe. In the 12 months prior to enrollment, 243 patients (50.1%) had visited the general practitioner (GP); 349 (72%) consulted a National Health Service (NHS) specialist; 68 (14%) utilized Emergency Care; and 50 (10.3%) had been admitted to hospital on account of asthma, with a total of 2059 work days lost. At the end of the 1-year survey, asthma severity changed as follows: 32.8% intermittent, 38.1% mild persistent, 23.7% moderate, and 4.3% severe, with a substantial drop in corresponding outcomes: 39.6% visited their GP, 51.5% visited an NHS specialist, 5.2% used Emergency Care, and 4.3% were admitted to hospital. Compared to baseline, the total average cost per patient decreased globally by 17.9% (p<0.001) after the 1-year survey. In conclusion, during the study period we observed a significant decline in health resources consumption and thus in asthma cost of illness, even though specific costs for the pharmaceutical treatment of asthma increased substantially. These results are likely due to a more strict control of patients and to their more appropriate clinical management.

Efficacy of pulmonary rehabilitation in chronic respiratory failure (CRF) due to chronic obstructive pulmonary disease (COPD): The Maugeri Study.

UNLABELLED: While the effectiveness of pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) is well established, its effectiveness in the most severe category of COPD, i.e. patients with chronic respiratory failure (CRF), is less well known. OBJECTIVE: To verify the effects of PR in patients with CRF, and compare the level of improvement with PR in these patients to that of COPDs not affected by CRF. METHODS: A multi-centre study was carried out on COPD patients with versus without CRF. The PR program included educational support, exercise training, and nutritional and psychological counselling. Lung function, arterial gases, walk test (6MWT), dyspnoea (MRC; BDI/TDI), and quality of life (MRF(28); SGRQ) were evaluated. RESULTS: Thousand forty seven consecutive COPD inpatients (327 with CRF) were evaluated. In patients with CRF all parameters improved after PR (0.001). Mean changes: FEV(1), 112 ml; PaO(2), 3.0 mmHg; PaCO(2), 3.3 mmHg; 6MWT, 48 m; MRC, 0.85 units; MRF(28) total score, 11.5 units. These changes were similar to those observed in patients without CRF. CONCLUSIONS: This study, featuring the largest cohort so far reported in the literature, shows that PR is equally effective in the more severe COPD patients, i.e. those with CRF, and supports the prescription of PR also in these patients.

A new questionnaire specifically designed for patients affected by chronic obstructive pulmonary disease; The Italian Health Status Questionnaire.

The aim of this study was to develop a specific and valid questionnaire for Italian COPD patients, living on the north or the south of Italy-which are two culturally distinct areas. The project consisted in three steps: (1) initial item set generation to identify items relevant to both genders, all ages and both regions; (2) item reduction including tests of regional specificity; (3) tests of internal validity using item-response theory using Rasch one-parameter modelling. Ninty-six COPD patients (mean aged 69 yr; 78 Male) completed the original set of 124 items of the Italian Health Status Questionnaire (IHSQ). Item reduction was carried out using an established standardised approach employing classical psychometric test theory. The internal construct validity of the 47 items that survived this process were tested to determine whether they constituted a unidimensional construct "impaired health due to COPD" using Rasch analysis. This showed that the questionnaire had very good psychometric properties, with an excellent Person Separation Index of 0.95 and no evidence of bias due to item-trait interaction (chi104(2)=127.1, P=n.s.). The combination of classical test theory and modern item-response methodology has produced a questionnaire with excellent measurement properties suitable for COPD patients whether from the north or south of Italy.

Impact of long-term ventilation on patients' health status.

Therapy and rehabilitation of common causes of respiratory-induced disability are directed towards a reduction of exacerbations, minimization of symptom severity, and improvement, or at least maintenance, of the patient's health. Unfortunately, these diseases are frequently complicated by chronic respiratory failure (CRF), which determines a rapid increase in the impact of the disease on the patient's daily life and well-being. Under such circumstances, the effect of therapy on a patient's health status and well-being represents the most important subjective outcome of treatment. An adequate assessment of patient's quality of life can only be obtained from the patients themselves; that is, it requires direct measurement through the use of valid and reliable questionnaires, whether generic or disease-specific. The St George's Respiratory Questionnaire and the Maugeri Foundation Respiratory Failure Questionnaire have been shown to be applicable and reliable in patients on long-term ventilation.

GP management of community-acquired pneumonia in Italy: the ISOCAP study.

BACKGROUND: Community-Acquired Pneumonia (CAP) is still a significant problem in terms of incidence, mortality rate, particularly in infants and the elderly, and socioeconomic burden. General Practitioners (GPs) are the first reference for patients with this disease, but there are few published studies regarding the outpatient treatment of CAP. METHODS: The ISOCAP study aimed to identify the type and outcome of the diagnostic-therapeutic management of CAP by GPs in Italy, within the framework of developing a closer interrelationship between GPs and pulmonary specialists. Thirty-six Pulmonary Divisions throughout Italy each contacted 5 local GPs who agreed to recruit the first 5 consecutive patients who consulted them for suspected CAP within the study's 1-year observation period. RESULTS: A total of 183 GPs took part in the study and enrolled, by the end of the observation period, 763 CAP patients; of these, complete data was available for 737 patients [males=373, females=364, mean age (+/- SD) 58.8 +/- 19.6 years]. 64.4% of patients had concomitant diseases, mainly systemic arterial hypertension and COPD. Diagnosis of CAP was based by GPs on physical examination only in 41.6% of cases; in the remaining chest X-ray was also performed. In only 4.6% of patients were samples sent for microbiological analysis. All patients were treated with antibiotics: 76.7% in mono-therapy, 23.3% with a combination of antibiotics. The antibiotic class most prevalently used in mono-therapy was cephalosporin, primarily ceftriaxone; the most frequently used combinations were cephalosporin + macrolide and cephalosporin + quinolone. Mono-therapy was effective in 70% of cases, the combination of two or more antibiotics in 91.2% of patients. Overall treatment efficacy was 94.7%; hospitalisation was required in 8.5% of cases. CONCLUSIONS: Outpatient management of CAP by GPs in Italy is effective, hospitalisation being necessary only in the most severe cases due to age, co-morbidities or extent of pneumonia. This signifies a very significant savings in national health costs.

CCR5 expression and CC chemokine levels in idiopathic pulmonary fibrosis.

CC chemokines play an important role in the pathogenetic mechanisms of interstitial lung disease, while a downregulation of CC chemokine receptor (CCR)5 in the fibrotic stages of sarcoidosis has been observed. To evaluate the involvement of CC chemokines and the expression of CCR5 in idiopathic pulmonary fibrosis (IPF) and, more specifically, in usual interstitial pneumonia, 35 subjects were studied. CC chemokine ligand (CCL)2, CCL3 and CCL4 levels were measured in the bronchoalveolar lavage fluid (BALF) of 18 nonsmoker control subjects and 17 patients affected by IPF. CCR5 expression was evaluated in alveolar macrophages and lymphocytes. The BALF levels of all chemokines were significantly increased in IPF: median (range) CCL3 1.6 (1.0-11.1) versus 1.2 (0.0-3.8) pg x mL(-1); CCL4 6.2 (1.3-96.0) versus 3.4 (0.3-6.8) pg x mL(-1); and CCL2 60.1 (16.7-251.3) versus 4.6 (0.5-119.4) pg x mL(-1). CCL2 levels correlated negatively with the carbon monoxide diffusing capacity of the lung (D(L,CO)) and arterial oxygen tension. CCR5 expression was significantly reduced in lymphocytes from IPF compared with controls. The CC chemokines investigated are involved in the inflammatory mechanisms of idiopathic pulmonary fibrosis, and the results are in agreement with the hypothesis of a downregulation of the T-helper 1 immunological response in this disease.

Cellular and molecular mechanisms in chronic obstructive pulmonary disease: an overview.

In the last decade, the analysis of bronchial biopsies and lung parenchyma obtained from chronic obstructive pulmonary disease (COPD) patients compared with those from smokers with normal lung function and non-smokers has provided new insights on the role of the different inflammatory and structural cells, their signalling pathways and mediators, contributing to a better knowledge of the pathogenesis of COPD. This review summarizes and discusses the lung pathology of COPD patients with emphasis on inflammatory cell phenotypes that predominate in different clinical conditions. In bronchial biopsies, a cascade of events takes place during progression from mild-to-severe disease. T lymphocytes, particularly CD8+ cells and macrophages are the prevalent inflammatory cells in the lung of healthy smokers and patients with mild COPD, while total and activated neutrophils predominate in severe COPD. The number of CD4+, CD8+ cells and macrophages expressing nuclear factor-kappa B (NF-kappaB), STAT-4 and IFN-gamma proteins as well as endothelial adhesion molecule-1 in endothelium is increased in mild/moderate disease. In contrast, activated neutrophils (MPO+ cells) and increased nitrotyrosine immunoreactivity develops in severe COPD. In bronchial biopsies obtained during COPD exacerbations, some studies have shown an increased T cell and granulocyte infiltration. Regular treatment with high doses of inhaled glucocorticoids does not significantly change the number of inflammatory cells in bronchial biopsies from patients with moderate COPD. The profile in lung parenchyma is similar to bronchial biopsies. 'Healthy' smokers and mild/moderate diseased patients show increased T lymphocyte infiltration in the peripheral airways. Pulmonary emphysema is associated with a general increase of inflammatory cells in the alveolar septa. The molecular mechanisms driving the lymphocyte and neutrophilic prevalence in mild and severe disease, respectively, needs to be extensively studied. Up-regulation of pro-inflammatory transcription factors NF-kappaB and STAT-4 in mild, activated epithelial and endothelial cells in the more severe disease may contribute to this differential prevalence of infiltrating cells.

STAT4 activation in smokers and patients with chronic obstructive pulmonary disease.

Activation of the transcription factor signal transducer and activator of transcription (STAT)-4 is critical for the differentiation of T-helper 1 cells/type-1 cytotoxic T-cells and the production of interferon (IFN)-gamma. Expression of STAT4, phospho-STAT4, IFN-gamma and T-box expressed in T-cells (T-bet) proteins in bronchial biopsies and bronchoalveolar lavage (BAL)-derived lymphocytes, obtained from 12 smokers with mild/moderate chronic obstructive pulmonary disease (COPD) (forced expiratory volume in one second (FEV1) 59 +/- 16% predicted), 14 smokers with normal lung function (FEV1 106 +/- 12% pred) and 12 nonsmoking subjects (FEV1 111 +/- 14% pred), was examined by immunohistochemistry and immunocytochemistry. In bronchial biopsies of COPD patients, the number of submucosal phospho-STAT4+ cells was increased (240 (22-406) versus 125 (0-492) versus 29 (0-511) cells mm(-2)) when compared with both healthy smokers and control nonsmokers, respectively. In smokers, phospho-STAT4+ cells correlated with the degree of airflow obstruction and the number of IFN-gamma+ cells. Similar results were seen in BAL (2.8 (0.2-5.9) versus 1.03 (0.09-1.6) versus 0.69 (0-2.3) lymphocytes x mL(-1) x 10(3)). In all smokers who underwent lavage, phospho-STAT4+ lymphocytes correlated with airflow obstruction and the number of IFNgamma+ lymphocytes. T-bet expression was not altered in bronchial biopsies and BAL-derived lymphocytes between the three groups. In conclusion, this study suggests that stable mild/moderate chronic obstructive pulmonary disease is associated with an active T-helper 1 cell/type-1 cytotoxic T-cell inflammatory process involving activation of signal transducer and activator of transcription 4 and interferon-gamma production.

Lower respiratory tract infections in chronic obstructive pulmonary disease outpatients with tracheostomy and persistent colonization by P. aeruginosa.

Outpatients with tracheostomy can be managed with a low risk for severe airways infections despite colonization with pathogenic bacteria. No studies have been focused on chronic obstructive pulmonary disease (COPD), a condition known for recurrent exacerbations. The aim of our study was to verify whether at follow-up in tracheostomized COPD versus other disease outpatients, persistent P. aeruginosa colonization may influence the rate and treatment of lower respiratory tract infections (LRTI) or hospital admissions. Thirty-nine outpatients were considered: 24 were affected by COPD (age 66, 54-78 years, mean, range), 15 by restrictive lung disease (RLD) (57, 41-72 years). During an 18-month follow-up the number of LRTIs were recorded. Bacterial identifications were assessed at baseline and every month for 6 months in bronchial aspirates. The number of LRTI per patient was not significantly different between COPD [37, 1(0-6)] and RLD [18, 1(0-5)], [total, median (range)]. Persistent P. aeruginosa colonized 18 COPD (75%), 12 RLD patients (86%) and was not associated with an increased number of LRTI: 1(0-6) and 1(0-2), respectively. There were no differences in the number of hospital admissions: COPD 0(0-2), RLD 1(0-1), with a significant decrease versus before tracheostomy (P < 0.001). In conclusion, the rate of LRTI and hospital admissions in COPD outpatients with chronic tracheostomy was low, similar to non-COPD patients and independent of P. aeruginosa colonization.

Anti-IgE monoclonal antibody: a new approach to the treatment of allergic respiratory diseases.

The immunoglobulin E (IgE) antibody plays a central role in the allergic immune responses. The ability to reduce circulating IgE with a humanized monoclonal antibody (omalizumab) represents a new therapeutic approach for the treatment of IgE-mediated allergic diseases. The use of an anti-IgE antibody in the treatment of asthma was first suggested in preliminary studies in which omalizumab demonstrated efficacy in attenuating both the early- and late-phase bronchial responses to inhaled aeroallergens. Therapy with omalizumab has demonstrated both a significant beneficial effect on a number of measures and a favorable safety profile. It reduces the frequency of asthma exacerbations and the need for inhaled corticosteroids (ICSs), and improves asthma symptoms, lung function, and quality of life. The anti-IgE approach to asthma treatment has several potential advantages, such as the treatment of other concomitant atopic diseases (allergic conjunctivitis and rhinitis, atopic dermatitis, and food allergy) regardless of atopiC of allergic sensitization.

Proliferation and inflammation in bronchial epithelium after allergen in atopic asthmatics.

BACKGROUND: The mechanisms that regulate epithelial integrity and repair in asthma are poorly understood. We hypothesized that allergen exposure could alter epithelial inflammation, damage and proliferation in atopic asthma. OBJECTIVE: We studied epithelial cell infiltration, shedding, expression of the proliferation marker Ki-67 and the epithelial cell-cell adhesion molecules Ep-CAM and E-cadherin in bronchial biopsies of 10 atopic mild asthmatics 48 h after experimental diluent (D) and allergen (A) challenge in a cross-over design. METHODS: Epithelial shedding, expressed as percentage of not intact epithelium, Ki-67+, eosinophil/EG-2+, CD4+ and CD8+ cells were quantified by image analysis in bronchial epithelium, and adhesion molecules were analysed semi-quantitatively. RESULTS: Epithelial shedding was not altered by A (D: 88.1+/-3.1% vs. A: 89.2+/-3.7%; P=0.63). The numbers of Ki-67+ epithelial (D: 10.2+/-0.2 vs. A: 19.9+/-0.3 cells/mm; P=0.03), EG-2+ (D: 4.3+/-0.5 vs. A: 27+/-0.3 cells/mm; P=0.04) and CD4+ cells (D: 1.7+/-1.2 vs. A: 12.3+/-0.6 cells/mm; P=0.04) were significantly increased after A, whilst CD8+ numbers were not significantly changed (P>0.05). E-cadherin and Ep-CAM epithelial staining showed a similar intensity after D and A (P>0.05). We found a positive correlation between EG-2+ and Ki-67+ cells in the epithelium (Rs: 0.63; P=0.02). CONCLUSION: Our study indicates that allergen challenge increases epithelial proliferation in conjunction with inflammation at 2 days after exposure. This favours the hypothesis that long-lasting epithelial restitution is involved in the pathogenesis of asthma.