Efficacy of daytime transcutaneous electrical stimulation of the genioglossus muscle in patients with obstructive sleep apnea syndrome: short report.

Obstructive sleep apnea syndrome (OSAS) is characterized by hypotonia of lingual and suprahyoid muscles. Genioglossus muscle is responsible for protrusion and depression of the tongue. Its dysfunction results in occlusion of the upper airways and greater incidence of apnea-hypopnea events during sleep. The aim of this prospective study was to compare the effects of daytime transcutaneous electrical stimulation of the genioglossus muscle and standard continuous positive airway pressure (CPAP) therapy on the quality of sleep, in patients with OSAS. During a 4-week study period, 19 patients with OSAS were subjected to daytime transcutaneous electrical stimulation of the genioglossus muscle before sleep and another 19 subjects underwent standard CPAP therapy. Polysomnography (apnea-hypopnea index, AHI), Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI) were used to diagnose OSAS and to verify the efficacy of both treatments. Electrical stimulation treatment was reflected by a decrease in PSQI (p = 0.012) but did not influence ESS and AHI values (p > 0.05). In turn, CPAP therapy resulted in a significant decrease in ESS and AHI values (p < 0.001) but exerted no effect on PSQI (p = 0.089). Despite improvement of sleep quality, electrical stimulation does not seem to reduce AHI values in patients with OSAS. Daytime electrical stimulation can be considered as an adjunct treatment in OSAS. Future prospective studies should center on the identification of patients with OSAS who may benefit most from transcutaneous electrical stimulation.

[Excessive daytime sleepiness and risk for obstructive sleep apnea in the public transport drivers]. / Ocena wystepowania wzmozonej sennosci w ciagu dnia oraz ryzyka obturacyjnego bezdechu podczas snu u kierowców zawodowych komunikacji miejskiej.

BACKGROUND: Obstructive sleep apnea (OSA) is a set of symptoms related to the increased upper airways resistance during sleep (due to pharyngeal walls collapse) leading to intermittent airflow obstruction in the lungs. One of the most severe OSA symptoms is excessive daytime sleepiness. Sustained daytime sleepiness may impair cognitive functions and thus influence the everyday functioning of affected person. MATERIAL AND METHODS: The aim of the study was to prospectively assess excessive daytime sleepiness and the risk for OSA in municipal bus drivers. The study was performed in a group of 103 men. The anonymous survey comprised Epworth Sleepiness Scale (ESS) for daytime sleepiness assessment and STOP-Bang Questionnaire (SBQ) for OSA risk assessment. RESULTS: In 43 (42%) respondents OSA risk was assessed as low, while moderate and high risk was observed in 55 (53%) and 5 (5%) drivers, respectively. Severe daytime sleepiness correlated positively with ESS results (r = 0.32; p < 0.05). In drivers with high OSA risk revealed in SBQ no correlation with high ESS was observed. CONCLUSIONS: In drivers with moderate and high OSA risk a sleep medicine specialist consultation with a consecutive diagnostic procedures is necessary. STOP-Bang Questionnaire and ESS are the fast tools to identify patients at increased risk for OSA.

Rehabilitation of patients with obstructive sleep apnea syndrome.

The current treatment of obstructive sleep apnea syndrome (OSAS) focuses on alleviation of symptoms by increasing airway patency during sleep through positive airway pressure, oral appliances, changes in sleep position, weight loss, or surgical treatment. Continuous positive airway pressure (CPAP) is currently the treatment of choice and prevents upper airway obstruction, resulting in improved sleep architecture and daytime symptoms. Despite proven efficacy, adherence to CPAP treatment is still not efficient. The new methods of rehabilitation (exercise training programs, hypoglossal nerve stimulation) for patients with OSAS are currently modified. The aim of the present study was to present recent developments in the field of selected aspects of rehabilitation in patients with OSAS. Database search was focused on exercise training programs and electrostimulation of genioglossus muscle. The search for articles on the rehabilitation interventions for OSAS was performed using the PubMed database from 1966 to 2013. Most of the findings have shown beneficial effects of rehabilitation. In detail, we describe the recent developments and potential adverse effects of electrostimulation and physical exercises. According to the results of studies presented, the above therapy might support conventional treatment or may be an alternative for patients with poor compliance to CPAP therapy, mandibular advancement devices, or ineffective results of surgical procedures as well.

[Treatment of chronic obstructive pulmonary disease--traditional bronchodilatation and targeted anti-inflammatory therapy]. / Leczenie przewleklej obturacyjnej choroby pluc--bronchodylatacja i przeciwzapalna farmakoterapia celowana.

Currently available pharmacological treatment of COPD relies mostly on prophylaxis (smoking cessation) and symptomatic treatment, i.e. inhaled anticholinergic agents, ß2-agonists and phosphodiesterase inhibitors, aiming in their bronchodilatation capacity. Inhaled corticosteroid therapy is mainly prescribed in far advanced stages of the disease and its role in disease modification is still controversial. The authors analize currently available treatment modalities with regards to their potential anti-inflammatory and pleiotropic mode of action, which may lead to disease course modification.

Utility of bronchoalveolar lavage in evaluation of patients with connective tissue diseases.

Pulmonary involvement is common in patients with connective tissue diseases (CTDs), and significantly contributes to morbidity and mortality in this patient population. There are different forms of lung pathology in CTDs, which include primary involvement such as interstitial lung disease or pulmonary hemorrhage, and pulmonary complications resulting from other CTD-related organ involvement including aspiration pneumonia due to muscle weakness or esophageal fibrosis. Moreover, iatrogenic lung disease, such as medication-induced hypersensitivity pneumonitis or opportunistic infections due to immunosuppression, may develop. Appropriate treatment of pulmonary complications in patients with CTDs requires careful diagnostic workup because different forms of lung involvement may overlap, causing similar clinical manifestations and similar radiological or functional impairment. Moreover, in view of the broad variability of clinical course of CTD-related interstitial lung disease, identification of biomarkers helpful in predicting prognosis becomes of key importance. In addition to radiological assessment and functional testing that provide information regarding localization and severity of lung disease, bronchoalveolar lavage (BAL) appears helpful in revealing the nature of lung pathology and intensity of lung inflammation through sampling of cells and fluid from the lower respiratory tract. The aim of this article is to critically review available data concerning the evaluation of BAL cytology in different forms of lung disease associated with CTDs.

Serum cathepsin K and cystatin C concentration in patients with advanced non-small-cell lung cancer during chemotherapy.

A pathogenic implication of cathepsin K (Cath K) and its inhibitor - cystatin C (Cyst C) occur to be of growing importance in the mechanisms of tumor invasiveness in lung cancer. This study was conducted to investigate the prognostic role and the effects of chemotherapy on serum Cath K and Cyst C (ELISA) in patients with advanced stage non-small cell lung cancer (NSCLC). The study entered 40 patients (32 men) and 15 healthy volunteers (control group). Peripheral blood samples were taken before and after four cycles of chemotherapy. The mean serum Cyst C levels were significantly higher in patients with advanced NSCLC than in controls (p=0.003). The levels of Cath K in serum of NSCLC are comparable to those in controls. No correlation was found between Cath K and Cyst C concentrations and the histological type and staging of lung cancer. Patients with T4-stage had a lower level of Cyst C, than those with T2 (p=0.033). No correlation was found between the concentrations of Cath K, Cyst C and the effect of chemotherapy. However, Cyst C level positively correlated with serum creatinine concentration (R=0.535; p=0.005) in patients who responded to chemotherapy and with patient's age (R=0.456; p=0.018) in whole group. When the cut-off values of serum Cath K and Cyst C (23.35 pmol/l, 1.29 mg/l, respectively) were used, the prognoses of high and low groups were not different. Concluding, patients with lung cancer have a higher serum concentration of Cyst C compared to healthy people. In our opinion, determination of Cath K and Cyst C concentrations has no clinical significance in the prognosis of the survival time in lung cancer.

Concentration of surfactant protein D, Clara cell protein CC-16 and IL-10 in bronchoalveolar lavage (BAL) in patients with sarcoidosis, hypersensivity pneumonitis and idiopathic pulmonary fibrosis.

The process of interstitial inflammation, often chronic, goes fluently from alveolitis through granuloma formation to irreversible fibrosis and lung remodeling. Eventually, the loss of functional alveolar units leads to chronic respiratory failure. The pneumoproteins (e.g. SP-D, CC-16) are considered to be markers of interstitial inflammation. We measured BAL concentration of SP-D, CC-16 and IL-10 in patients with sarcoidosis (27), IPF (7) and HP (9). The level of each marker was determined by ELISA specific kit. We found the highest SP-D and CC-16 BAL concentration in patients with the III stage of sarcoidosis (96,67 ng/ml and 31,78 ng/ml, respectively). The lowest SP-D concentration was observed in patients with IPF (76,49 ng/ml), and the lowest CC-16 concentration in patients with HP (21,39 ng/ml). The differences were not statistically significant. In the group of the III stage of sarcoidosis higher SP-D levels were related to higher BAL cytosis and higher percentage of BAL neutrophils, just the opposite as in the IPF and HP group. In the III stage of sarcoidosis and HP, the lower SP-D levels, the lower FEV1 and VC values. The results show, that in acute interstitial inflammation with larger parenchyma engagement (III stage of sarcoidosis) the levels of SP-D were higher then in chronic interstitial inflammation (IPF).

Serum levels of angiopoietin-1, angiopoietin-2, and their receptor tie-2 in patients with nonsmall cell lung cancer during chemotherapy.

This pilot study was conducted to investigate the prognostic role and the effects of chemotherapy on serum angiogenic factors enzyme-linked immunosorbent assay consisting of Angiopoietin-1 and 2 (Ang-1, Ang-2) and their receptor Tie-2 in patients with advanced stage nonsmall cell lung cancer (NSCLC). Concentration of Ang-2 was higher in NSCLC (n= 40) than in healthy people (n= 15), whereas Ang-1 and Tie-2 were comparable. In our opinion determination of Ang-1, Ang-2, and Tie-2 concentrations have no clinical significance in the prognosis of the survival time in lung cancer and can not be used as a predictor of response to the chemotherapy.

Serum levels of HMGB1, survivin, and VEGF in patients with advanced non-small cell lung cancer during chemotherapy.

Recently, several reports have suggested that HMGB1 (the high-mobility group box-1) plays a key role in tumor angiogenesis through multiple mechanisms, including up-regulation of proangiogenic factors. This study was conducted to investigate the prognostic role and the effects of chemotherapy on serum (ELISA) angiogenic factors: HMGB1, survivin and VEGF (Vascular Endothelial Growth Factor) in patients with advanced stage non-small cell lung cancer (NSCLC). The study entered 40 patients (31 man) and 15 healthy volunteers (control group). Peripheral blood samples were taken before and after four cycles of chemotherapy. The mean serum HMGB1 and VEGF levels were significantly higher in patients with advanced NSCLC than in controls (p=0.024, p=0.028, respectively). The levels of survivin in NSCLC patients were comparable to controls. No correlation was found between HMGB1, survivin and VEGF concentrations and the histological type and staging of lung cancer. Similarly, no correlation was revealed between the concentrations of HMGB1, survivin and VEGF and the effect of chemotherapy. However, in patients with NSCLC, HMGB1 positevely correlated with survivin (R=0.814, p=0.007) before chemotherapy, and negatively with VEGF (R=-0.841, p=0.035) after chemotherapy. When the cut-off values of serum HMGB1, survivin and VEGF (2.38 ng/ml, 81.92 pg/ml, 443.26 pg/ml, respectively) were used, the prognoses of high and low groups were not different. Concluding, patients with NSCLC have a higher serum concentration of HMGB1 and VEGF, while survivin levels are comparable to healthy individuals. In our opinion, determination of HMGB1, survivin and VEGF concentrations has no clinical significance in the prognosis of the survival time in lung cancer.

Thiocyanate concentration in saliva of cystic fibrosis patients.

Thiocyanates (SCN-) are ubiquitous in nature. There are indispensable part of host defense system that act as a substrate for lactoperoxidase (LPO). In our study we present initial data on SCN- concentration in saliva of CF patients in comparison to healthy non-smokers and healthy smokers. 5 ml of saliva was collected from each subject to a sterile tube and thiocyanate concentration was measured in each sample. The results of the measurements are presented on Fig. 1. Mean concentration of SCN- in saliva of CF patients was 0.031 +/- 0.0052 g/l, in healthy non-smokers 0.039 +/- 0.0048 g/l and in healthy smokers 0.048 +/- 0.0161 g/l. The differences between each group were statistically significant. Studies on larger group of patients and probably on different material (BALF or induced sputum) should present interesting data complementing the in vitro studies.

[Tuberculosis pulmonum--"threaten us of epidemic"?]. / Gruzlica pluc--"czy grozi nam epidemia"?

Tuberculosis (TB) remains a deadly infectious disease affecting millions of people worldwide with 95% of cases and 98% of deaths occuring in developing countries (9 milion new cases, 1 million deaths annually) vs.WHO. Tuberculosis is on the increase in developed countries, because of AIDS, the use of immunosuppresive drugs which depress the host defence mechanism, decreased socioeconomic conditions, as well as increased immigration of persons from areas of high endemicity. The major reason for this increase was because of rapid rise in cases from sub-Saharan Africa (due to AIDS) nad Russia. Incidense of tuberculosis in Poland 2007--the number of notified cases was 8014. Pulmonary cases represented 92.7% of total all TB cases and 628 cases of extrapulmonary TB. Chidren TB cases represented 0.9% (74 cases) of all cases notified in Poland. The incidence of tuberculosis increases with age from 1.1 in children do 41.2 among 65 and older. The incidence of men (31.5) was two times higher than in women--14.5 per 100 000 respectivly. There were 716 deaths due to pulmonary TB and 23 from extrapulmonary TB. Multidrug resistance (MDR) of Mycobacterium tuberculosis is a major therapeutic problem, in the world, with a high mortality and occurs mainly in HIV-infected patients. The WHO estimates that around 50 million people are infected with MDR-TB! WHO suggest that a greater investment in the establishment treatment strategy of DOTS (Directly Observed Treatment Short-course) into all posible regions.

[Histone dependent signalization during pharmacotherapy of chronic obstructive pulmonary disease]. / Sygnalizacja zalezna od histonów w farmakoterapii przewleklej obturacyjnej choroby pluc.

Chronic obstructive pulmonary disease (COPD) is a 4(th) major cause of morbidity and mortality worldwide. Cigarette smoking and oxidative/nitrosative stress leading to chronic inflammation is considered as a major cause of COPD but up to now, details of molecular pathways responsible for development of disease are unknown. Recent reports indicate the role of disruption in histone function in promoting synthesis of inflammatory cytokines through increased gene transcription which underlies disease development. Core histone acetylation/deacetylation regulate their transcription activity and drug induced changes of its intensity may be an interesting field of further research. In this article the opinions about the role of steroids as inhibitors of the inflammatory process as well as resistance to steroids have been presented. Findings from studies which aimed to explore the anti-inflammatory activity of drugs such as theophylline and N-acetylcysteine and their ability to suppress oxidative stress may suggest the usefulness of these drugs in causative treatment of COPD. However, further studies are necessary to confirm these findings.

Serum levels of VEGF-C, VEGF-D, and sVEGF-R2 in patients with lung cancer during chemotherapy.

The aim of this study was to assess serum levels of vascular endothelial growth factor C and D (VEGF-C, VEGF-D) and soluble VEGF receptor 2 (sVEGFR-2) in patients with lung cancer during chemotherapy. The study included 80 patients (64 men and 16 women; mean age 61.1) diagnosed histologically with lung cancer. Forty-four (55%) had non-small cell lung cancer (NSCLC) and 36 (45%) had small cell lung cancer (SCLC). Squamous cell carcinoma was established in 56% (25 patients) of all patients with NSCLC, adenocarcinoma in 20% (9 patients), and non-small cell lung cancer in 23% (10 patients). The control group consisted of 20 healthy volunteers. Peripheral blood samples were taken before and after four cycles of chemotherapy. VEGF-C, VEGF-D, and sVEGFR-2 levels were assessed by ELISA method. Serum levels of VEGF-C and VEGF-D were significantly higher in both NSCLC and SCLC groups in comparison with controls. VEGF-C concentration decreased after chemotherapy, whereas VEGF-D concentration was at the same level. No correlation was found between VEGF-C and VEGF-D concentrations and the effect of treatment. Patients with lung cancer and progression after chemotherapy (PD) had the higher concentration of sVEGFR-2 than patients with partial remission (PR). The levels of sVEGFR-2 were lower before and after treatment than in controls. No relation was found between VEGF-C, VEGF-D, and sVEGFR-2 concentrations and the histological type and staging of lung cancer. Summing up, serum concentrations of VEGF-C and VEGF-D were higher in patients with lung cancer both before and after chemotherapy than in healthy controls, whereas sVEGFR-2 concentration was lower than in healthy controls. An increase in concentration of sVEGFR-2 during chemotherapy may suggest progression of the disease. However, it requires further examination.

[Posttranslational p53 phosphorylation in non small cell lung cancer cells after radio/chemotherapy]. / Potranslacyjna fosforylacja bialka p53 w komórkach niedrobnokomórkowego raka pluca po radio-i chemioterapii

INTRODUCTION: p53 protein is a critical regulator of cell cycle and apoptosis. Many stimuli change its expression and modify its functions. The aim of our work was to determine stability and chosen posttranslational modification of p53 protein during the treatment of lung cancer. MATERIAL AND METHODS: We investigated levels of poly-ADP-ribose- a marker of cellular DNA damage, DNA ploidy, Ki-67 expression, wild type and mutated p53 protein expression and intensity of phosphorylation of chosen p53 serine sites: C-terminal Ser392, and N-terminal Ser15, and Ser20 in fiberoptic bronchoscopy biopsy samples taken from patients suffering from recurrent squamous cell lung cancer before and after radio/chemotherapy. Analysis was based on results obtained from 23 patients after surgery in I-IIIA clinical stage of the disease. RESULTS: Therapy lowered the number of G2/M cells, but increased S fraction cell population in about 50%. Therapy increased p53 expression and p53 phosphorylation at Ser392 and Ser20, and these changes correlated with poly-ADP-ribose levels and Ki-67 expression. CONCLUSIONS: Our results indicate that apart from changes in p53 quantity, p53 posttranslational phosphorylation play a role in regulation of neoplastic cells proliferation in response to drugs.

[Stenting central airways with tracheobronchial stents]. / Protezowanie tchawicy i duzych oskrzeli z zastosowaniem stentów tchawiczo-oskrzelowych.

Tracheobronchial stenting is indicated in the palliative care of cancer patients with central airways obstruction due to primary chest and neck tumors, metastatic and congenital lesions of these organs. Stents, tubular prostheses, solid or wired, removable or not, of different shape, size, material, are used to treat airway obstructions due to endobronchial overgrowing, infiltration, compression, or relaxation of the airway walls. Silicone stents are well tolerated and removable. Their limitations are: the mucociliary clearance impairment, thick walls, displacement possibility. Rigid bronchoscopy is required for insertion of the prosthesis. Metal stents allow mucociliary transport, exactly match the trachea or bronchus dimension and are insertable with the bronchofiberscope. Attempts of self-absorbed stents application in the course of tracheobronchomalacia and post surgical bronchial wall collapse are being made. The choice of the type of the stent used is made on the basis of personnel experience, type and localisation of the obstruction, clinical status and accompanying diseases.

[Pathogenesis of chronic obstructive pulmonary disease. Molecular mechanisms (part II)]. / Patogeneza przewleklej obturacyjnej choroby pluc. Czesc II. Podloze molekularne.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Smoking is considered the major cause of the disease. Relatively little is known about the molecular mechanisms underlying inflammatory response in smokers' lungs and how this relates to the susceptibility to the disease, particularly why only 10-15% of smokers develop COPD. Recent development in molecular biology techniques allowed the insight into the inner space of the cell, to the levels far beyond the reach of the traditional methods. We review recent hypotheses on cellular and molecular background of COPD with emphasis on the potential role of histone acetylation, as a key modulator of enhanced gene transcription responsible for proinflammatory cytokines production in COPD. Authors propose a role for modification of nucleosomal structure in inflammatory cytokine gene transcription in response to smoking. Cigarette smoke causes oxidative stress altering the balance between histone deacetylation and acetylation in favor of acetylation. This can contribute to the airflow obstruction in smokers susceptible to the development of COPD. Furthermore, histone acetylation seems to be a potential mechanism exclusive to smokers with susceptibility to COPD based on the transcription of specific pro- and anti-inflammatory cytokine combinations.

Serum levels of IGF-I and IGFBP-3 in patients with lung cancer during chemotherapy.

The aim of this study was to assess serum levels of insulin-like growth factors (IGF-I and IGFBP-3) in patients with lung cancer during chemotherapy. The study included 38 patients (33 males and 5 females; mean age 59.8) diagnosed histologically with lung cancer. Twenty-five patients (65%) had non-small cell lung cancer (NSCLC) and 13 patients (35%) had small cell lung cancer (SCLC). Squamous cell carcinoma was established in 30% (11 patients) of all patients with NSCLC, adenocarcinoma in 13% (5 patients), and non-small cell cancer in 36% (9 patients). The control group consisted of 10 healthy volunteers. Peripheral blood samples were taken before and after four cycles of chemotherapy. IGF-I and IGFBP-3 levels were assessed by ELISA method. Serum levels of IGF-I measured before chemotherapy were significantly higher in both NSCLC and SCLC groups in comparison with controls. No significant differences were observed in serum IGF-I levels before and after four cycles of chemotherapy. The levels were still high after chemotherapy in patients with NSCLC and SCLC. Serum levels of IGFBP-3 were markedly lower in patients with NSCLC both before and after treatment compared to controls. No significant differences were found in patients with NSCLC before and after cytoreduction treatment. Prior to treatment, serum IGFBP-3 levels were significantly lower in patients with SCLC in comparison with controls. After cytoreduction treatment, the levels were decreased when compared to controls but without statistical significance. In conclusion, both before and after chemotherapy serum levels of IGF-I were significantly higher, whereas IGFBP-3 levels were lower in patients with NSCLC and SCLC compared to controls. Chemotherapy had no influence on the serum levels of IGF-I and IGFBP-3. Neither a histological type of NSCLC nor clinical staging had any effect on the serum levels of IGF-I and IGFBP-3.

[Pathogenesis of chronic obstructive pulmonary disease. Cellular mechanisms (part I)]. / Patogeneza przewleklej obturacyjnej choroby pluc. Czesc i. podloze komórkowe.

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. Smoking is considered the major cause of the disease. All smokers develop airway inflammation through oxidative stress with macrophages, neutrophiles, lymphocytes, eosinophils, NK-cells and mediators involved. Macrophages through the activation of Nuclear Factor kappa B (NF.-kappaB) release proinflammatory mediators, lymphocyte chemotactic agents and elastolytic enzymes, activate neutrophil driven serine proteases and GM-CSF. Neutrophiles release IL-8 which in turn recruits neutrophils to the airways. In response to cigarette smoke lung epithelium may release TNF-alpha, TGF-beta, IL-1beta, GM-CSF, IL-8 reactive oxygen species (ROS). Increased number of lymphocyte T CD8+ and CD4+ subpopulations may lead to lung epithelium cells apoptosis and necrosis through perphorines and granzyme-B and TNF-alpha activation. Moreover, increased expression of IL-6, IL-10, IL-12, IL-13, and INF-gamma is observed. Authors indicate the possibility of new treatment strategies such as: agents directed against adhesion molecules, chemokines, phosphodiesterase 4, p38 MAPK, NF.-kappaB phosphoinositide-3-kinase gamma, TGF-beta, NOS synthase, serine proteinases and matrix metalloproteinases.

[The effect of fenspiride on the number of exacerbations and the time of first exacerbation in patients with chronic bronchitis]. / Wplyw fenspirydu na liczbe zaostrzen i czas ich wystapienia u chorych na przewlekle zapalenie oskrzeli.

UNLABELLED: The aim of the work was evaluation of efficacy of fenspiride b.i.d. on the number of exacerbations and the time to the first exacerbation in patients with chronic bronchitis. MATERIAL AND METHODS: Randomized, multicentre study controlled versus placebo was carried out in 12 centers in Poland. All patients, 89 females and 68 males aged between 20 and 74, were treated with fenspiride at the dose of 160 mg/day for a period of 6 months. The following symptoms were recorded every month in order to evaluate the therapeutic efficacy: sputum quality and quantity, cough intensity, dyspnea and bronchospasm. Based on these symptoms diagnosis of exacerbation was performed according to American Thoracic Society criteria. RESULTS: Quality and quantity of sputum and cough significantly improved in the fenspiride group (comparing to the placebo group p= 0.027 and p = 0.049 adequately for sputum and cough). A significant difference between groups was observed in the number of exacerbation episodes and their duration. In the fenspiride group there were 0.53 episodes of exacerbation compared with 1.12 episodes in the placebo group (p = 0.038). Mean duration of exacerbation was 3.3 days in the fenspiride group and 7.3 days in the placebo treated patients (p = 0.034). Time to the first exacerbation differed between groups, but this difference was not statistically significant. Number of side effects observed did not differ between groups. CONCLUSION: Fenspiride treatment was assessed as relatively effective in terms of influence on exacerbations, and well tolerated during six month therapy.