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Effect of pharmacotherapy on rate of decline of lung function in chronic obstructive pulmonary disease. Tiotropium as a first maintenance drug in COPD: Changes in forced expiratory volume in 1 second over time in COPD. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. A 4-year trial of tiotropium in chronic obstructive pulmonary disease.

Respir Res , Tiotropium versus salmeterol for the prevention of exacerbations of COPD. LancetRespir Med , 1 7: Choice of bronchodilator therapy for patients with COPD. Tiotropium in combination with placebo, salmeterol, or fluticasone-salmeterol for treatment of chronic obstructive pulmonary disease. Mechanisms of dyspnea during cycle exercise in symptomatic patients with GOLD stage I chronic obstructive pulmonary disease. Long-acting beta-agonists in the management of chronic obstructive pulmonary disease: Correlating changes in lung function with patient outcomes in chronic obstructive pulmonary disease: Inhaled formoterol dry powder versus ipratropium bromide in chronic obstructive pulmonary disease study group.

Comparison of the efficacy, tolerability, and safety of formoterol dry powder and oral, slow release theophylline in the treatment of COPD. Rossi A, Polese G: Aclidinium bromide for the treatment of chronic obstructive pulmonary disease. Efficacy and safety of aclidinium bromide compared with placebo and tiotropium in patients with moderate-to-severe chronic obstructive pulmonary disease: Buhl R, Banerji D: In chronic obstructive pulmonary disease, a combination of ipratropium and alburerol is more effective than either agent alone.

An day multicenter trial. The impact of combined inhaled bronchodilator therapy in the treatment of COPD. Effects of tiotropium with and without formoterol on airflow obstruction and resting hyperinflation in patients with COPD. Comparison of a combination of tiotropium plus formoterol to salmeterol plus fluticasone in moderate COPD. QVA demonstrates superior bronchodilation compared with indacaterol or placebo in patients with chronic obstructive pulmonary disease. Karner C, Cates CJ: Long-acting beta2-agonist in addition to tiotropium versus either tiotropium or long-acting beta2-agonist alone for chronic obstructive pulmonary disease.

Concurrent use of indacaterol plus tiotropium in patients with COPD provides superior bronchodilation compared with tiotropium alone: Combination bronchodilator in the management of chronic obstructive pulmonary disease. Lancet Respir Med , 1: Dual bronchodilation with QVA versus single bronchodilator therapy: Susceptibility to exacerbation in chronic obstructive pulmonary disease.

Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. The impact of tiotropium on mortality and exacerbations when added to inhaled corticosteroids and long-acting - agonist therapy in COPD. Roflumilast —an oral anti-inflammatory treatment for chronic obstructive pulmonary disease: Effect of 1-year treatment with roflumilast in severe chronic obstructive pulmonary disease.

Roflumilast in symptomatic chronic obstructive pulmonary disease: Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with long acting bronchodilators: Phosphodiesterase-4 inhibitor therapy for lung diseases. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease.

Proposal for a multidimensional staging system for chronic obstructive pulmonary disease. Respir Med , Derivation and validation of a composite index of severity in chronic obstructive pulmonary diseases. Expansion of the prognostic assessment of patients with chronic obstructive pulmonary disease: Rossi A, Zanardi E: Multidimensional indices and clinical phenotypes in COPD. Long term domiciliary oxygen therapy in chronic hypoxic corpulmonale complicating chronic bronchitis and emphysema.

Nocturnal Oxygen Therapy Trial Group: Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: One year period prevalence study of respiratory acidosis in acute exacerbations of COPD: Page 14 of 16 6. A randomized trial of strategies for assessing eligibility for long-term domiciliary oxygen therapy. The Italian multicentre study on noninvasive ventilation in chronic obstructive pulmonary disease patients. Lung volume reduction as an alternative to transplantation for COPD.

Clin Chest Med , Heart and lung transplantation in the United States, — Am J Transplant , 7: Double- and single-lung transplantation: Guidelines for the physiotherapy management of the adult medical, spontaneously breathing patients. Thorax , 64 suppl: Percorsi riabilitativi nelle malattie respiratorie. Statement on pulmonary rehabilitation. Associazione Italiana Pneumologi Ospedalieri: Raccomandazioni sulla Riabilitazione Respiratoria. RassPatol App Respir , European Society of Intensive Care Medicine: Physiotherapy for adult patients with critical illness: Intensive Care Medicine , California pulmonary Rehabilitation Collaborative Group: Effects of pulmonary rehabilitation on dyspnea, quality of life, and healthcare costs in California.

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Antibiotics in addition to systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease. Canadian Thoracic Page 15 of 16 Society recommendation for management of chronic obstructive pulmonary disease - update. Nava S, Fanfulla F: Ventilazione meccanica non invasiva. Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Respiratory intermediate care units: Impact of a hospitalbased home-care program on the management of COPD patients receiving long-term oxygen therapy. Randomised controlled trial of home based care of patients with chronic obstructive pulmonary disease.

An official American Thoracic Society clinical policy statement: Palliative and end of life care for patients with severe COPD. Cure palliative dei pazienti con patologie respiratorie croniche avanzate non oncologiche. Piano Sanitario Nazionale — Home telemonitoring for respiratory conditions: Am J Manag Care , EurRespir J , Impact of a hospital-based home-care program on the management of COPD patients receiving long-term oxygen therapy.

Randomised controlled trial of homebased care of patients with chronic obstructive pulmonary disease. Socio-technical and organizational challenges to wider e-Health implementation. ChronRespir Dis , 6: Tele-assistance in chronic respiratory failure patients: A pilot trial of telemedicine-assisted, integrated care for patients with advanced amyotrophic lateralsclerosis and their caregivers. J TelemedTelecare , Celli B, MacNee W, and committee members: Screening for chronic obstructive pulmonary disease using spirometry: The clinical and integrated management of COPD. Submit your next manuscript to BioMed Central and take full advantage of: Multidisciplinary Respiratory Medicine , 8: Guidelines advise annual influenza vaccination in chronic asthma.

Vaccination rate was Using binary logistic regression, the predictors for vaccination in were patient advice Odds ratio [OR] On analyzing the responses from the second questionnaire at one year after attendance to asthma clinic, predictors changed to compliance to medication OR 9.

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Out of the 46 unvaccinated patients in , 27 had asthma exacerbations before and 19 patients had exacerbations in Symptomatic asthma patients are more likely to be vaccinated. One year after the first contact, treatment compliance and previous asthma exacerbations gained statistical significance as predictors of vaccination. Asthma, Influenza, Vaccine Background Evidence shows that influenza vaccination leads to decreased hospitalization from influenza complications, fewer deaths during the influenza season, decreased healthcare costs in the elderly in the general population [1], and a decreased number of lost workdays and physician visits in healthy adults [2].

Some studies suggest that, at least in children, the vaccine decreases asthma exacerbations [3], however in adults, a meta-analysis of published studies has failed to demonstrate a significant decrease in asthma exacerbations [4]. Despite this lack of evidence, the Global Initiative for Asthma GINA guidelines issued in December , advise that patients with moderate to severe asthma should receive influenza vaccination every year or at least when vaccination of the general population is advised.

This is an open access article distributed under the terms of the Creative Commons Attribution License http: The Advisory Committee on Immunization Practices ACIP recommends annual influenza vaccination for adults and children with chronic disorders of the pulmonary or cardiovascular systems, including asthma. At this hospital the asthma clinics are run by Consultant Respiratory physicians, who together with specialist trainees in respiratory medicine and general medicine, see to patients attending these clinics.

The clinics are run with the help of a nurse. Many asthma patients are followed up in the community, however most of the more severe cases are referred to the asthma clinic for follow up. The aim of this study was to determine the uptake of the influenza vaccine in a group of patients with moderate to severe chronic asthma and to try to establish the main predictors of vaccination. Data collected included age, gender, asthma control, whether patients had been advised to receive the influenza vaccine or not, and if so by whom.

Patients were also asked about comorbidities such as chronic kidney disease, for which guidelines also advise influenza vaccination. Asthma control was assessed by frequency of salbutamol use or reliever medication, the need for systemic steroids or nebulized treatment, and hospitalization over the past 12 months. After patients had filled in the questionnaire, participants received advice on the importance of influenza vaccination in asthma patients.

The following year, in February , the same patients were contacted by telephone and the same questionnaire was used, in order to follow up and compare results with the previous year. At least two attempts were made to contact each patient. Patients were considered to have well-controlled asthma if they rarely or never required their reliever salbutamol inhaler, and did not need hospitalization, oral steroids or nebulized treatment over the previous year.

Page 2 of 6 Compliance was assessed by asking patients how often they forgot to take their medication. Those who never or rarely forgot to take their asthma treatment were defined as compliant, while patients who forgot to take their treatment more than once a week or on a daily basis were defined as being non-compliant.

Patients with incomplete questionnaires were excluded from the study. Binary logistic regression and Stepwise regression was determined using Minitab 16 software. Data protection approval was deemed sufficient from an ethical point of view. Consent was obtained from all the Consultant Respiratory physicians in the hospital to interview asthma patients under their care.

Consent to perform the questionnaires was obtained from all patients. Results A total of patients females, 43 males, mean age This is a Table 1 shows the characteristics of the original patients by gender. The mean age for those taking the vaccine was In Table 2, binary logistic regression and stepwise regression show patient advice and female gender as predictors for taking the vaccine, while comorbidity and a history of previous side effects to the vaccine are shown to be the main negative predictors for vaccination.

Figure 1 shows the reasons asthma patients gave for taking the influenza vaccine that winter. Figure 2 shows the reasons given by the patients for not taking the vaccine patients were given the option of choosing more than one reason. Out of these, 22 Non vaccinated patients needed 0.

Unfortunately data prior to vaccination was not available. Discussion This study showed that despite the recommendation for influenza vaccination in asthma guidelines, just under half of the patients with asthma failed to take the influenza vaccine. The decision whether to take it or not is influenced by several factors including trust or mistrust in modern medicine, perceived side-effects from prior vaccination, perceived risk associated with influenza [5], and concern that vaccination may induce exacerbations of asthma. A randomized controlled trial RCT involving 2, adults with asthma [6], and a large multicentre cohort study [7] concluded that influenza vaccination in asthma is safe.

In our study, the reported influenza vaccination rate of This study was carried out on patients attending a hospital asthma clinic; therefore patients were likely to suffer from more severe asthma compared to patients treated in primary care. The power of this study was insufficient to gauge the impact of vaccination as there was an insignificant difference in exacerbation rates before and after vaccination for individual vaccinated patients. However, there was a significantly higher asthma exacerbation rate in vaccinated patients when compared to unvaccinated patients.

Though not reaching statistical significance, non-vaccinated patients seemed to use more short-acting reliever medication. This could reflect the possibility that patients with more severe symptoms are more likely to vaccinate against influenza. On the contrary, it is also possible that those patients with less severe or more intermittent asthma are less likely to Figure 2 Reasons given by patients for not taking influenza vaccine in winter.

Furthermore, perhaps more reliance on reliever medication reflected a different behavioural attitude which was not otherwise assessed in this study. Unvaccinated patients reported a lower number of exacerbations in the second year. This was probably the result of new attendants to the asthma clinic who besides being offered vaccination could have their asthma better controlled with medication.


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While this reason is speculative, this explanation is supported by the emergence of compliance to medication and the occurrence of previous exacerbations as a predictor for vaccination after one year of attendance to the asthma clinic. Using binary logistic regression in the first questionnaire, advice to the patient, and patient gender were the best predictors of vaccination, while presence of comorbidities and having experienced previous vaccine side effects were the negative predictors. Because of this, it is possible that women could be more aware of influenza risk and the necessity to vaccinate themselves.

Other factors have been shown to affect influenza vaccination in asthma, including increased vaccination rates with age [11]. In this study while the mean age of vaccinated patients was higher than in non-vaccinated patients, logistic regression failed to show it as a predictor, while stepwise regression re-instated it.

This may have occurred because the stepwise regression model used only 5 statistically significant predictors out of the 9 predictors evaluated, removing the possible confounders of age. Logistic regression had evaluated all the 9 predictors. In the first questionnaire, receiving advice to vaccinate heavily predicted influenza vaccination, but this effect was greatly decreased in the second questionnaire as probably many patients with a mindset not to vaccinate had also received advice during the first questionnaire, thus leveling off the difference between vaccinated and non vaccinated individuals.

However, one year after attendance to the asthma clinic the second questionnaire produced two new predictors, namely: This indicates that overall, patients at the asthma clinic were not only advised to receive the influenza vaccine, but their asthma treatment was also optimized. Indeed all patients on direct questioning highly rated the impact of physician advice on their decision to vaccinate. Medical literature confirms that physician recommendations and education about influenza vaccine availability, effectiveness, and adverse effects [12] were other factors which were found to influence parents to vaccinate their asthmatic children.

Both logistic regression and stepwise regression showed that the most consistent negative predictor was the occurrence of past side effects to the influenza vaccine. Notwithstanding this, a significant proportion of patients do actually vaccinate despite having experienced previous vaccine side effects.

This may reflect that side effects are often minor when compared to the fear of major attacks of acute asthma. This reason is supported by the fact there was a greater likelihood for severely affected patients to vaccinate. Public Health vaccination campaigns tend to target mainly the elderly population, who are more likely to suffer from comorbidities. The study cannot offer an explanation for this result, except that this may be a possible reason for an increased fear of side effects of vaccination.

The main limitations of the study were that information on whether the patient had been vaccinated or not during the previous 12 months was obtained by self-report. The statistical power was too low to give an indication of the potential benefit of vaccination on the control of asthma symptoms.

Furthermore, the hospital environment might have influenced respondents to praise the effect of medical advice and perhaps overestimate their compliance to medication. Fear of sideeffects and the presence of comorbidities were negative predictors of vaccination.

While this study could not assess the effectiveness of the vaccine in preventing severe attacks, patients with more severe symptoms are more likely to vaccinate against influenza. One year after the first questionnaire, compliance to medication and occurrence of a previous exacerbation became a positive predictor of vaccination. Around a fourth of patients with asthma still vaccinate against influenza despite the previous occurrence of side effects.

Page 6 of 6 Influenza vaccination uptake and socioeconomic determinants in 11 European countries. Vaccine , 27 Asthma and influenza vaccination. Findings from the — national health interview surveys. Chest , 3: Parental perspectives on influenza vaccination among children with asthma. Public Health Rep , 2: Predictors of seasonal influenza vaccination in chronic asthma. Multidisciplinary Respiratory Medicine 8: Competing interest The authors declare that they have no competing interest.

JB Data inputting and data analysis. MB study design, supervision of the study, data analysis, statistics, drafting and revision of manuscript. All authors read and approved the final manuscript. Acknowledgements Nursing staff at medical outpatients who helped distribute the questionnaires to patients attending asthma clinic. The efficacy and cost effectiveness of vaccination against influenza among elderly persons living in the community. Effectiveness and cost-benefit of influenza vaccination of healthy working adults, a randomized controlled trial.

JAMA , Vaccine safety Datalink team: J Paediatr , 3: Vaccines for preventing influenza in people with asthma. Cochrane Database Syst Rev Telford R, Rogers A: A qualitative study, health education research. Educ Res , 18 6: The American lung association asthma clinical research centres: The safety of inactivated influenza vaccine in adults and children with asthma. Does influenza vaccination exacerbate asthma?

Analysis of a large cohort of children with asthma. Vaccine safety datalink team. Arch Fam Med , 9: Influenza vaccination among adults with asthma. Am J Prev Med , 37 2: Influenza vaccination in patients with asthma: Br J Gen Pract , 57 SP-D is a specific biomarker for monitoring COPD, assessment of exacerbation frequency and arrangement of treatment modalities.

In the present study, we aimed to investigate the correlation between serum and induced sputum SP-D levels with severity and acute exacerbations of COPD. All subjects performed pulmonary function tests. Induced sputum samples were obtained to determine SP-D level. COPD patients were followed up for acute exacerbations for 6 months.

Serum SP-D levels of group 3 were the highest and induced sputum SP-D levels of group 2 were the lowest among the three groups. Our study demonstrates the adverse effects of smoking on local SP-D levels since low levels of induced sputum SP-D were found in the group of current smokers, who were not receiving inhaled corticosteroid treatment. Chronic obstructive pulmonary disease, Induced sputum, Surfactant protein-D Background Chronic obstructive pulmonary disease COPD is a complex chronic inflammatory disease that involves the activity of various inflammatory cells and mediators [1].

Both local and systemic inflammatory reactions are observed in COPD. There are ongoing researches trying to find out different markers in COPD course. SP-D is a 43kDa member of the collectin family that is produced from collagenous glycoprotein in type II pneumocytecells. SPD is a protein responsible for homeostasis which has an important protective role in the immune system against inhaled microorganisms and allergens. It plays a part in protection against viral, bacterial, and fungal infections, as well as apoptotic cells [2].

Akinci Ozyurek et al. SP-D level declines as the disease progresses. The association between decreased SP-D level in lungs and smoking has also been demonstrated in previous studies [5,6]. Therefore, SP-D is a promising biomarker that might help to determine the health status of patients with lung diseases, particularly with respect to progression of dyspnea and decreasing pulmonary functions.

Therefore, in the present study we aim to investigate the relationships between COPD severity and acute exacerbations frequency with serum and induced sputum SP-D levels. Written informed consent was obtained from each participating patient and control subjects prior to the study. Our study sample comprised of 60 subjects in total: In our study all patients and control subjects performed pulmonary function tests PFT.

Induced sputum specimen was obtained and also tested for induced sputum SP-D level. COPD patients were followed for 6 months to determine exacerbation frequency. The data concerning the exacerbation frequency were collected via hospital visits and telephone calls. Measurement of biochemical parameters Venous blood sample was obtained from each patient. Serum samples were prepared by collecting blood in a vacuum tube and allowing it to clot for 30 minutes at room temperature.

The detection limit was 0. The inter- and intra-assay variability were 8. Twenty healthy individuals having normal PFTs and 40 patients diagnosed as mild, moderate, severe, and very severe COPD based on the current Global Initiative for Chronic Obstructive Lung Disease GOLD guidelines using postbroncodilatator FEV1 values post bronchodilator values were obtained after mcg salbutamol inhalation , were enrolled in the study [7].

Induced sputum analysis The patients were informed about the process and FEV1 values were measured before the bronchodilatation. This was continued for a period up to 20 minutes by incremental doses applied with Akinci Ozyurek et al. The induction started using 0. The induction was carried out for 30 seconds, 1 minute, and 5 minutes.

Induction with higher concentration was not applied to patients when adequate material could be obtained at this concentration. Induction with a higher concentration was not applied to patients when adequate material could be obtained at this concentration. Following each induction, participants were asked to rinse their mouth with water and produce sputum by cough. The processing of induced sputum The induced sputum was immediately analyzed following the acquirement. Firstly, the specimen was weighed. Sputum was treated with Sputalysin 0.

The resulting filtrate was weighed. The cell viability of the filtrate was evaluated by Trypan blue and total cell count TCC was calculated on a Thoma slide. TCC was calculated by following the formula: The resultant supernatant was separated and put into Falcon tubes.

Page 3 of 7 Statistical analysis The statistical analyses of our study were performed using SPSS statistical software version The variables were investigated using visual histograms, probability plots and analytical methods Kolmogorov-Simirnov test to determine the normality of distributions. For continuous variables without normal distribution Mann—Whitney U test was used for the comparison of the two groups patients receiving inhaler steroids or not receiving inhaler steroids , whereas Kruskal-Wallis test for the comparison of parameters between 3 groups.

T- test was used for the comparison of parameters with normal distribution between 2 groups and ANOVA together with Bonferroni correction was used for the comparison of continuous parameters with normal distribution among the three groups. The parameters affecting 6 month exacerbation frequency, induced sputum and serum surfactant protein D levels were investigated using Spearman correlation analysis.

Multiple linear regression models were used to identify independent predictors of 6 month exacerbation frequency, serum and induced sputum surfactant protein D levels. The model fit was assessed using appropriate residual and goodness of fit statistics. Results The demographic characteristics, PFT parameters and complete blood count results of our study groups are reported in Table 1.

Smoking status active, ex-smoker of the groups was also evaluated. Mean duration of inhaled steroid treatment was 5. The serum and sputum SP-D values of subjects in all three groups were compared Table 3. Although, induced sputum SP-D levels in Group 2 were the lowest, they did not achieve to the significance level. In the literature review, no study including both induced sputum and serum SP-D measurement in COPD patients has been found according to our knowledge.

Induced sputum analysis has been recently recognized as a valuable method for revealing the pathogenesis of inflammatory airway diseases such as COPD and asthma, and monitoring the activity and treatment response in these pathologies []. Currently, induced sputum is recognized to reflect lower respiratory tract inflammation [10,13].

Therefore, we preferred to use induced sputum specimens, also known as cost-effective diagnostic tool, in evaluating the courses of local and systemic inflammation in COPD. Previous studies have demonstrated a positive correlation between cigarette consumption pack year and serum SP-D levels. Serum SP-D concentrations have been found to be higher in current smokers than in exsmokers [2,14]. In our study, among COPD patients, there was a negative correlation between induced sputum SP-D levels and cigarette consumption pack year , whereas serum SP-D levels and cigarette consumption pack year showed a positive correlation.

The comparison of induced sputum SP-D levels among three groups revealed no statistically significant difference. Sputum SP-D concentrations of Group 2 were lowest among study groups. Inhaled corticosteroid treatment was more common in Group 3 due to increased airway obstruction level and exacerbation frequency of severe and very severe COPD patients. Sputum SP-D levels were significantly different between patients with and without inhaled corticosteroid therapy in the present study. Moreover, significant correlation was also found between number of years on inhaled corticosteroid treatment and induced sputum SPD levels in linear regression analysis.

These results also support the fact that the use of inhaled corticosteroids indirectly contributes to the local SP-D levels in a positive way [15]. Coefficient B Standard Error t p Constant Different results might be due to the fact that study populations and medications in the study by Ishiwaka et al. Group 2 had higher serum SP-D levels than Group 1, although, these differences did not reach to significance level. We believe that low number of patients in all groups was a limitation for the statistical comparison.

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