Picturing asthma in Turkey: results from the Turkish adult asthma registry.

INTRODUCTION: National data on asthma characteristics and the factors associated with uncontrolled asthma seem to be necessary for every country. For this purpose, we developed the Turkish Adult Asthma Registry for patients with asthma aiming to take a snapshot of our patients, thereby assigning the unmet needs and niche areas of intervention. METHODS: Case entries were performed between March 2018 and March 2022. A web-based application was used to record data. Study outcomes were demographic features, disease characteristics, asthma control levels, and phenotypes. RESULTS: The registry included 2053 patients from 36 study centers in Turkey. Female subjects dominated the group (n = 1535, 74.8%). The majority of the patients had allergic (n = 1158, 65.3%) and eosinophilic (n = 1174, 57.2%) asthma. Six hundred nineteen (32.2%) of the patients had obese asthma. Severe asthma existed in 670 (32.6%) patients. Majority of cases were on step 3-5 treatment (n: 1525; 88.1%). Uncontrolled asthma was associated with low educational level, severe asthma attacks in the last year, low FEV1, existence of chronic rhinosinusitis and living in particular regions. CONCLUSION: The picture of this registry showed a dominancy of middle-aged obese women with moderate-to-severe asthma. We also determined particular strategic targets such as low educational level, severe asthma attacks, low FEV1, and chronic rhinosinusitis to decrease uncontrolled asthma in our country. Moreover, some regional strategies may also be needed as uncontrolled asthma is higher in certain regions. We believe that these data will guide authorities to reestablish national asthma programs to improve asthma service delivery.

COVID-19: vaccination vs. hospitalization.

OBJECTIVE: Vaccination is the most efficient way to control the coronavirus disease 2019 (COVID-19) pandemic, but vaccination rates remain below the target level in most countries. This multicenter study aimed to evaluate the vaccination status of hospitalized patients and compare two different booster vaccine protocols. SETTING: Inoculation in Turkey began in mid-January 2021. Sinovac was the only available vaccine until April 2021, when BioNTech was added. At the beginning of July 2021, the government offered a third booster dose to healthcare workers and people aged > 50 years who had received the two doses of Sinovac. Of the participants who received a booster, most chose BioNTech as the third dose. METHODS: We collected data from 25 hospitals in 16 cities. Patients hospitalized between August 1 and 10, 2021, were included and categorized into eight groups according to their vaccination status. RESULTS: We identified 1401 patients, of which 529 (37.7%) were admitted to intensive care units. Nearly half (47.8%) of the patients were not vaccinated, and those with two doses of Sinovac formed the second largest group (32.9%). Hospitalizations were lower in the group which received 2 doses of Sinovac and a booster dose of BioNTech than in the group which received 3 doses of Sinovac. CONCLUSION: Effective vaccinations decreased COVID-19-related hospitalizations. The efficacy after two doses of Sinovac may decrease over time; however, it may be enhanced by adding a booster dose. Moreover, unvaccinated patients may be persuaded to undergo vaccination.

Regional distribution of genetic mutation in lung cancer in Turkey (REDIGMA).

INTRODUCTION: The results of standard chemotherapy in lung cancer are not very satisfactory, so it is important to identify genetic mutations that provide targeted therapies. Recent reports have suggested influences of racial difference on the frequency of mutation in lung cancer. We aimed to determine the frequency and regional distribution of genetic mutations of non-small cell lung cancer (NSCLC) in Turkey. MATERIALS AND METHODS: Regional distribution of genetic mutations in lung cancer in Turkey (REDIGMA) study was carried out as a prospective, cross-sectional, observational study in a large number of centers in which lung cancer patients were followed and could perform genetic mutation analysis on patients' biopsy materials. RESULT: The 703 patients (77.7% male, mean age 63.3 ± 12.5 years) who were diagnosed as NSCLC from 25 different centers were included in the study. Tumor samples from patients were reported as 87.1% adenocarcinoma, 6.4% squamous cell carcinoma and 6.5% other. Mutation tests were found to be positive in 18.9% of these patients. The mutations were 69.9% EGFR, 26.3% ALK, 1.6% ROS and 2.2% PDL. Mutations were higher in women and non-smokers (p<0.000, p<0.001). Again, the frequency of mutations in adenocarcinoma was higher in metastatic disease. There was no difference between the patient's age, area of residence, comorbidity and clinical stage and mutation frequency. CONCLUSIONS: Our study revealed that the EGFR mutation rate in Turkey with NSCLC was similar to East European, African-American and Caucasian patients, and was lower than in East Asia.

Sleep disturbances in patients with lung cancer in Turkey.

INTRODUCTION: Sleep quality is known to be associated with the distressing symptoms of cancer. The purpose of this study was to analyze the impact of cancer symptoms on insomnia and the prevalence of sleep-related problems reported by the patients with lung cancer in Turkey. MATERIALS AND METHODS: Assesment of Palliative Care in Lung Cancer in Turkey (ASPECT) study, a prospective multicenter study conducted in Turkey with the participation of 26 centers and included all patients with lung cancer, was re-evaluated in terms of sleep problems, insomnia and possible association with the cancer symptoms. Demographic characteristics of patients and information about disease were recorded for each patient by physicians via face-to-face interviews, and using hospital records. Patients who have difficulty initiating or maintaining sleep (DIMS) is associated with daytime sleepiness/fatigue were diagnosed as having insomnia. Daytime sleepiness, fatigue and lung cancer symptoms were recorded and graded using the Edmonton Symptom Assessment Scale. RESULT: Among 1245 cases, 48.4% reported DIMS, 60.8% reported daytime sleepiness and 82.1% reported fatigue. The prevalence of insomnia was 44.7%. Female gender, patients with stage 3-4 disease, patients with metastases, with comorbidities, and with weight loss > 5 kg had higher rates of insomnia. Also, patients with insomnia had significantly higher rates of pain, nausea, dyspnea, and anxiety. Multivariate logistic regression analysis showed that patients with moderate to severe pain and dyspnea and severe anxiety had 2-3 times higher rates of insomnia. CONCLUSIONS: In conclusion, our results showed a clear association between sleep disturbances and cancer symptoms. Because of that, adequate symptom control is essential to maintain sleep quality in patients with lung cancer.

Frequency of Exacerbations and Hospitalizations in COPD Patients Who Continue to Smoke.

We evaluated the frequency of exacerbations and hospitalizations in chronic obstructive pulmonary disease (COPD) patients who continue to smoke.: We retrospectively analyzed the medical records of the COPD patients treated in Chest Diseases Clinic of Kocaeli University School of Medicine in 2007-2013. Their demographic characteristics, smoking status (non-smoker, current smoker, ex-smoker), Charlson Comorbidity Index (CCI), and history of COPD exacerbation and hospitalizations were evaluated. The cases of 120 patients (11 females, 9.2%; 109 males, 90.8%) were analyzed. Sixteen (13.3%) of the patients were current smokers, and 104 patients were ex-smokers (n=99) or non-smokers (n=5). The mean age was 69.7±7.9 years in the ex-smokers and 62.94±6.8 years in the current smokers. There were no significant differences between the current and ex-smokers regarding smoking history, FEV1 value, frequencies of exacerbations and hospitalization per year, or duration of follow-up. The initial stage of the COPD and the frequency of exacerbations were significantly correlated (p=0.003). The CCI values were significantly higher in the ex-smokers compared to current smokers (p=0.02). A correlation analysis of age, hospitalization and CCI revealed that age was significantly correlated with the hospitalization rate (p=0.02). Older age and the presence of comorbidities in ex-smokers might explain the similar rates of exacerbation and hospitalization between these current and ex-smokers.

Asthma-chronic obstructive pulmonary disease overlap: Results from a national-multicenter study.

Introduction: Patients with asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) have a greater disease burden than those with COPD or asthma alone. In this study, it was aimed to determine the prevalence, risk factors, and clinical features of ACO because there are limited national data in Türkiye. Materials and Methods: The study was conducted in a cross-sectional design in nine tertiary-care hospitals. The patients followed with a diagnosis of asthma or COPD for at least one year were enrolled in the study. The frequency of ACO and the characteristics of the patients were evaluated in the asthma and COPD groups. Result: The study included 408 subjects (F/M= 205/203, mean age= 56.24 ± 11.85 years). The overall prevalence of ACO in both groups was 20.8% (n= 85). The frequency was higher in the COPD group than in the asthma group (n= 55; 33.3% vs. n= 22; 9.8%), respectively (p= 0.001). Patients with ACO had similarities to patients with COPD in terms of advanced age, sex, smoking, exposure to biomass during childhood, being born in rural areas, and radiologic features. Characteristics such as a history of childhood asthma and allergic rhinitis, presence of chronic sinusitis, NSAID hypersensitivity, atopy, and high eosinophil counts were similar to those of patients with asthma (p<0.001). The annual decline in FEV1 was more prominent in the ACO group (mean= -250 mL) than in the asthma (mean change= -60 mL) and COPD (mean change= -230 mL) groups (p= 0.003). Conclusions: This study showed that ACO was common among patients with asthma and COPD in tertiary care clinics in our country. ACO should be considered in patients with asthma and COPD who exhibit the abovementioned symptoms.

Charlson Comorbidity Index in Predicting Poor Clinical Outcomes and Mortality in Patients with COVID-19.

OBJECTIVE: As known, older age and comorbidities are associated with poor clinical outcomes in patients with coronavirus disease 19. The aim of this study was to investigate the effect of the Charlson Comorbidity Index in predicting poor clinical outcomes in coronavirus disease 19 patients. MATERIAL AND METHODS: Demographic characteristics and poor clinical outcomes (presence of pneumonia, respiratory failure, intensive care unit admission, and mortality) of the patients were evaluated retrospectively. Classical and modified Charlson Comorbidity Index was calculated and adjusted according to age. RESULTS: In this study, 106 women and 107 men were included. The comorbidity rate was 50.7% and the most common comorbidities were hypertension (21.6%) and diabetes mellitus (15%). The rates of respiratory failure, intensive care unit admission, and mortality were 15%, 2.3%, and 2.8%, respectively. Older age was a high risk for poor outcomes. Pneumonia (odds ratio: 6.6; 95% CI: 3.4-12.7), respiratory failure (odds ratio: 5.2; 95% CI: 2.03-13.2), and intensive care unit admission (odds ratio: 1.1; 95% CI: 1.01-1.1) were significantly higher in patients with comorbid diseases than patients without any comorbidity (P < .05). Both median-modified and classical Charlson Comorbidity Index and their age-adjusted scores were significantly higher in patients with poor outcomes. CONCLUSIONS: It is suggested that evaluation of the Charlson Comorbidity Index might contribute to the management of the patients with coronavirus disease 19 by predicting risk group for poor clinical outcomes and mortality.

Awareness and Knowledge of COVID-19 Among Health Care Workers in Early Phase of COVID-19 Pandemic.

OBJECTIVE: The study aims to evaluate the awareness and knowledge of COVID-19 among healthcare workers. MATERIAL AND METHODS: A questionnaire was applied to healthcare workers working at Kocaeli University Faculty of Medicine and University of Kyrenia, Dr. Suat Günsel Hospital, to evaluate the coronavirus disease 2019 awareness and level of knowledge. RESULTS: A total of 598 healthcare workers participated in the study. Two-thirds of the respondents were from Turkey, while one-third were from the Turkish Republic of Northern Cyprus. The general symptoms of coronavirus disease 2019 were well known in the general population. Awareness of most symptoms was significantly lower in the Turkish Republic of Northern Cyprus group. It was well known that coronavirus disease 2019 can be asymptomatic in some patients and it can be contagious. The necessity of wearing surgical masks on sick individuals was less known in the Turkish Republic of Northern Cyprus group (96.6% vs 61.6%; P = .000). While handwashing was found similar in both groups for protection from coronavirus disease 2019 transmission, social distance and mask recommendations were lower in the Turkish Republic of Northern Cyprus group (P < .05). The concern about transmitting the virus to themselves and their relatives was more significant in the Turkish Republic of Northern Cyprus group than the Turkey group (84.4% vs 96.5%; P = .000). And 92.2% of the healthcare workers thought they should stay in an alternative place instead of their homes. CONCLUSION: The awareness and knowledge level of coronavirus disease 2019 is higher in Turkey than in Turkish Republic of Northern Cyprus related to the increased number of coronavirus disease 2019 cases in Turkey. Continuous education programs can contribute to improving the level of knowledge and reducing anxiety.

The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort.

Background and objectives: Although several repurposed antiviral drugs have been used for the treatment of COVID-19, only a few such as remdesivir and molnupiravir have shown promising effects. The objectives of our study were to investigate the association of repurposed antiviral drugs with COVID-19 morbidity. Methods: Patients admitted to 26 different hospitals located in 16 different provinces between March 11-July 18, 2020, were enrolled. Case definition was based on WHO criteria. Patients were managed according to the guidelines by Scientific Board of Ministry of Health of Turkey. Primary outcomes were length of hospitalization, intensive care unit (ICU) requirement, and intubation. Results: We retrospectively evaluated 1,472 COVID-19 adult patients; 57.1% were men (mean age = 51.9 ± 17.7years). A total of 210 (14.3%) had severe pneumonia, 115 (7.8%) were admitted to ICUs, and 69 (4.7%) were intubated during hospitalization. The median (interquartile range) of duration of hospitalization, including ICU admission, was 7 (5-12) days. Favipiravir (n = 328), lopinavir/ritonavir (n = 55), and oseltamivir (n = 761) were administered as antiviral agents, and hydroxychloroquine (HCQ, n = 1,382) and azithromycin (n = 738) were used for their immunomodulatory activity. Lopinavir/ritonavir (ß [95% CI]: 4.71 [2.31-7.11]; p = 0.001), favipiravir (ß [95% CI]: 3.55 [2.56-4.55]; p = 0.001) and HCQ (ß [95% CI]: 0.84 [0.02-1.67]; p = 0.046) were associated with increased risk of lengthy hospital stays. Furthermore, favipiravir was associated with increased risks of ICU admission (OR [95% CI]: 3.02 [1.70-5.35]; p = 0.001) and invasive mechanical ventilation requirement (OR [95% CI]: 2.94 [1.28-6.75]; p = 0.011). Conclusion: Our findings demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such agents without proven clinical evidence might not be the best approach for COVID-19 treatment.

[Smoking prevalence in Kocaeli]. / Kocaeli'de sigara içme prevalansi

A questionnaire was performed in order to determine smoking prevalence in the target population just before the initiation of a social responsibility project which is aimed to increase the smoking cessation rates in Kocaeli. The sample selection was made based on population numbers in 12 town of Kocaeli city and smoking habits of population over the age of 18 were evaluated by a questionnaire survey by phone. There was 2721 person included in the study. The overall prevalence of active smokers was 32.3% (n= 902) and ex-smokers was 21.5% (n= 587). There was no statistical significance of smoking prevalence among towns except the lower smoking rates in Gebze (25.7%). The percentage of the current smokers was 42.5% in male population which was significantly higher than females (21.8%). The highest smoking prevalence was found between the ages of 35-44 (41.2%) while the lowest prevalence was observed in the subjects older than 55 years (19.8%). The mean age for smoking initiation was 19 years (17-20) and daily cigarette consumption was 17 sticks. Previous attempts for quitting smoking were found in 67.7% of current smokers. The mean number of smoking cessation attempts was 3 times and the mean duration of cessation was 5 months. The most common reason for smoking cessation was health issues. Eighty percent of cases harnessed their willpower to stop smoking while only 5% of them received medical treatment. It is suggested that determination of demographic features of the smokers might constitute a corner stone for smoking cessation projects.

The predictors of COVID-19 mortality in a nationwide cohort of Turkish patients.

The COVID-19-related death rate varies between countries and is affected by various risk factors. This multicenter registry study was designed to evaluate the mortality rate and the related risk factors in Turkey. We retrospectively evaluated 1500 adults with COVID-19 from 26 centers who were hospitalized between March 11 and July 31, 2020. In the study group, 1041 and 459 cases were diagnosed as definite and highly probable cases, respectively. There were 993 PCR-positive cases (66.2%). Among all cases, 1144 (76.3%) were diagnosed with non-severe pneumonia, whereas 212 (14.1%) had severe pneumonia. Death occurred in 67 patients, corresponding to a mortality rate of 4.5% (95% CI:3.5-5.6). The univariate analysis demonstrated that various factors, including male sex, age ≥65 years and the presence of dyspnea or confusion, malignity, chronic obstructive lung disease, interstitial lung disease, immunosuppressive conditions, severe pneumonia, multiorgan dysfunction, and sepsis, were positively associated with mortality. Favipiravir, hydroxychloroquine and azithromycin were not associated with survival. Following multivariate analysis, male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were found to be independent risk factors for mortality. Among the biomarkers, procalcitonin levels on the 3rd-5th days of admission showed the strongest associations with mortality (OR: 6.18; 1.6-23.93). This study demonstrated that the mortality rate in hospitalized patients in the early phase of the COVID-19 pandemic was a serious threat and that those patients with male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were at increased risk of mortality; therefore, such patients should be closely monitored.

Case Series of COVID-19 Presenting with Massive Hemoptysis.

Coronavirus disease 2019 (COVID-19) is a novel viral infection that has led to a global pandemic. The clinical spectrum of COVID-19 has a wide range from asymptomatic disease to severe disease, including acute respiratory distress syndrome and death. The most common symptoms are fever, cough, myalgia, and fatigue. Diarrhea, headache, sore throat, and hemoptysis are rare symptoms. There is no patient with COVID-19 presenting with massive hemoptysis in the literature. Here we present a case series of 3 patients with COVID-19 who were admitted to the emergency department with massive hemoptysis without any other symptoms.

Clinicopathologic significance of eosinophilic pleural effusions in a population with a high prevalence of tuberculosis and cancer.

OBJECTIVE: To reveal the diagnostic and prognostic significance of eosinophilic pleural effusions (EPEs) and assess their clinical implications. STUDY DESIGN: Seventy EPEs from 60 patients among 697 consecutive pleural effusions were investigated from 1996-2005 at Kocaeli University Hospital, Kocaeli, Turkey. Koss and Light's criteria were applied in the analysis, which comprised macroscopic, cytopathologic, biochemical and microbiologic examinations. RESULTS: Overall, cancerous underlying conditions were diagnosed in 22 patients (13 malignant and 9 paramalignant), 36.7% of EPEs. Benign causes were found in 43.3% (26 of 60) of the patients. Twelve pleural effusions (20.0%) were idiopathic. The comparison of pleural fluid and peripheral blood findings disclosed no significant difference among the various subgroups. CONCLUSION: EPE could be associated with inflammatory, benign, cancerous and paramalignant conditions. A closer search for a definite causes is warranted in the setting of EPEs, especially in populations with a high prevalence of tuberculosis and malignancy, such as in Kocaeli, Turkey, an industrial city in a developing country.

[The effect of postgraduate education on COPD knowledge level of primary care physicians]. / Mezuniyet sonrasi egitimin pratisyen hekimlerin KOAH ile ilgili bilgi düzeyine etkisi.

Besides chest disease specialists, primary care physicians also have a great role in prevention and treatment of chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the knowledge levels of primary care physicians about COPD before and after post graduate course. The level of knowledge was evaluated by a questionnaire including questions about COPD definition, prevalence, etiology, pathology, diagnostic methods, physical examination findings and treatment. Then a postgraduate course was performed about COPD and questionnaire forms were refilled. Ninety two physicians filled the questionnaire forms before and after seminar. Fifty of the physicians were female, 42 were male, mean age was 33.7 +/- 8.5 and duration of profession was 9.6 +/- 8 years. Thirty-six (39.2%) of physicians have attended a post graduate seminar on COPD previously. All physicians answered the questions about the most dominant sex that COPD was seen and etiologic agents correctly. Most of the physicians answered the questions about diseases that defined as COPD, pathology and physical examination findings incorrectly. There was no difference in number of correct answers between the physicians who have previously attended a post graduate seminar or not. Duration of profession was not correlated with correct answers. After the seminar, the number of correct answers increased significantly. Since most of the physicians answered the questions which are quite important in primary care such as COPD definition and physical examination findings incorrectly, it is thought that post graduate seminars about COPD should be performed more frequently. After the seminar, we observed significant increase in correct answers however long-term stability of this knowledge is needed to be determined in future studies.

The effect of positive airway pressure therapy on neurocognitive functions, depression and anxiety in obesity hypoventilation syndrome.

BACKGROUND: The aim of this study is to evaluate the presence of neurocognitive dysfunctions, depression and anxiety and the effect of positive airway pressure (PAP) therapy on these alterations in Obesity Hypoventilation Syndrome (OHS) patients. METHODS: Ten healthy normal and obese controls, 10 OHS and 10 OSAS patients were included in the study. Short form-36, Beck Depression Scale and State-Trade Anxiety Inventory (STAI 1-2) were performed. Wisconsin Card Sorting Test (WCST), Montreal Cognitive Assessment Scale (MOCA), Enhanced Cued Recall (ECR) and Mini Mental Test (MMT) were used for neurocognitive evaluation. All tests were repeated after one night PAP therapy in OHS and OSAS groups. RESULTS: OHS patients had the lowest scores of physical (PF) and social functioning (SF) in SF-36. The total number of persistent errors and incorrect answers were the highest in OHS group in WCST. The scores of MOCA, ECR and MMT were lower; depression and anxiety scores were higher in OHS group than in controls (p = 0,00). There was a significant increase in the completed categories in OHS after PAP therapy (p = 0,03). There were also significant increases in MOCA, ECR and MMT scores and significant decreases in depression and anxiety scores with respect to PAP therapy. CONCLUSIONS: Cognitive dysfunction, depression and anxiety are important under-recognized comorbidities in OHS. It is suggested that short term PAP therapy had positive effects on neurocognitive functions, depression and anxiety but further multicentre, prospective studies with large number of cases are needed to evaluate the effect of long term PAP therapy on these parameters.

Effects of erdosteine on smoking-induced lipid peroxidation in healthy smokers.

AIM: Oxidative stress caused by smoking has been implicated in many pulmonary diseases. Smoking causes reductions in plasma nitrate plus nitrite (NOx) concentrations and increases in plasma malondialdehyde (MDA) concentrations, which indicate oxidative stress and lipid peroxidation, respectively. In this study, we investigated the acute effects of smoking a single cigarette on the plasma concentrations of NOx and thiobarbituric acid reactive substances (TBARS) including MDA, and whether administration of erdosteine, a mucolytic and antioxidant agent, affects these parameters. METHODS: Thirty healthy smokers were included in the study. Subjects smoked a single cigarette in 10 minutes on the study day. For analysis of NOx, TBARS and cotinine, blood was drawn from each subject before and 5 and 30 minutes after smoking. The subjects were then randomly divided into two groups, one receiving placebo and the other erdosteine suspension 175mg/5mL twice daily for 1 month. After this treatment period, the same study protocol was carried out. Two subjects in the placebo and five subjects in the study group were excluded because of noncompliance. RESULTS: Twenty-three (14 female, 9 male) subjects completed the study. Their mean age was 32 +/- 8 years and their smoking history was 14 +/- 9 pack-years. Baseline NOx, TBARS and cotinine concentrations were similar between the groups. NOx concentrations decreased significantly after smoke exposure. At the end of the treatment period there were no significant differences in NOx, TBARS or cotinine concentrations between the groups. The concentration of TBARS after smoking decreased significantly in the erdosteine-treated group (at 5 minutes: 2.8 +/- 0.5 micromol/L before treatment and 2.3 +/- 0.3 micromol/L after treatment, p < 0.05; at 30 minutes: 2.8 +/- 0.5 micromol/L before treatment and 1.8 +/- 0.7 micromol/L after treatment, p < 0.05). Smoking history was significantly correlated with cotinine concentrations. CONCLUSION: Acute smoke exposure decreased plasma NOx concentrations in healthy smokers, and this was not changed with erdosteine treatment. However, significant decreases were noted in TBARS concentrations after smoke exposure in the group that received erdosteine, suggesting that short-term erdosteine administration might help prevent smoking-induced lipid peroxidation.

Effects of Different Combined Bronchodilator Therapies on Airway Inflammation in COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterised by chronic progressive airway obstruction and inflammation. Only a few studies have evaluated the effects of bronchodilator therapy on airway inflammation in patients with COPD. OBJECTIVE: The aim of this study was to investigate the effects of different combinations of bronchodilator therapies on airway inflammation in COPD. METHODS: Thirty patients with COPD and ten healthy nonsmoker subjects were included in the study. COPD patients were randomly classified into three groups. Groups 1, 2 and 3 were treated with ipratropium bromide plus formoterol (IP + FOR), theophylline plus ipratropium bromide (IP + THEO), and formoterol plus theophylline (FOR + THEO), respectively, for 12 weeks. Pulmonary function tests were performed, blood was drawn for arterial blood gas analyses, and sputum was induced before and after treatment. The induced sputum total and differential cell counts, serum and sputum inflammatory markers including interleukin (IL)-8, tumour necrosis factor (TNF)-alpha and leukotriene (LT)-B4 were measured. RESULTS: When compared with the control group, total sputum cell counts, number of neutrophils, and sputum and serum inflammatory marker levels were significantly higher in COPD patients. Although there were no statistically significant differences among the groups, inflammatory parameters were found to be significantly reduced in all three treatment groups at the end of treatment. Total cell counts were: 2.4 +/- 0.9 versus 1.28 +/- 0.5 x 10(6)cells/g in the IP + FOR group (p < 0.05), 2.32 +/- 0.4 versus 1.37 +/- 0.6 x 10(6)cells/g in the IP + THEO group (p < 0.05), and 3.05 +/- 1.3 versus 1.6 +/- 0.8 x 10(6)cells/g in the FOR + THEO group (p < 0.05). Sputum IL-8 levels were: 1738.5 +/- 292 versus 848 +/- 262 ng/L in the IP + FOR group (p < 0.05), 1543.2 +/- 378 versus 800.2 +/- 224 ng/L in the IP + THEO group (p < 0.05), and 1561.2 +/- 412 versus 815.7 +/- 259 ng/L in the FOR + THEO group (p < 0.05). CONCLUSION: Different combinations of bronchodilator therapies caused significant changes in sputum and blood IL-8, TNF-alpha and LTB4 levels of COPD patients without significantly improving pulmonary function tests or arterial blood gas parameters.