Successful Use of Easyhaler® Dry Powder Inhaler in Patients with Chronic Obstructive Pulmonary Disease; Analysis of Peak Inspiratory Flow from Three Clinical Trials.

INTRODUCTION: There is increasing pressure to use environmentally friendly dry powder inhalers (DPI) instead of pressurized metered-dose inhalers (pMDI). However, correct inhalation technique is needed for effective inhaler therapy, and there is persistent concern whether patients with chronic obstructive pulmonary disease (COPD) can generate sufficient inspiratory effort to use DPIs successfully. The aims of this study were to find clinical predictors for peak inspiratory flow rate (PIF) and to assess whether patients with COPD had difficulties in generating sufficient PIF with a high resistance DPI. METHODS: Pooled data of 246 patients with COPD from previous clinical trials was analyzed to find possible predictors of PIF via the DPI Easyhaler (PIFEH) and to assess the proportion of patients able to achieve an inhalation flow rate of 30 l/min, which is needed to use the Easyhaler successfully. RESULTS: The mean PIF was 56.9 l/min and 99% (243/246) of the study patients achieved a PIF ≥ 30 l/min. A low PIF was associated with female gender and lower forced expiratory volume in 1 s (FEV1), but the association was weak and a statistical model including both only accounted for 18% of the variation seen in PIFEH. CONCLUSIONS: Based on our results, impaired expiratory lung function or patient characteristics do not predict patients' ability to use DPIs in COPD; 99% of the patients generated sufficient PIFEH for successful dose delivery. Considering the targets for sustainability in health care, this should be addressed as DPIs are a potential option for most patients when choosing the right inhaler for the patient. TRIAL REGISTRATION: Two of three included trials were registered under numbers NCT04147572 and NCT01424137. Third trial preceded registration platforms and therefore, was not registered.

Validation of the Finnish severe respiratory insufficiency questionnaire.

INTRODUCTION: Chronic respiratory insufficiency impacts patients' lives and reduces quality of life. The Severe Respiratory Insufficiency (SRI) questionnaire examines health-related quality of life and is designed specifically for patients receiving home mechanical ventilation (HMV) for chronic respiratory failure (CRF). OBJECTIVES: The aim of this study was to validate the Finnish version of the SRI and study its reproducibility in patients with CRF. METHODS: Our 74 patients receiving HMV or long-term oxygen treatment for CRF or both completed the SRI and St George's Respiratory questionnaires (SGRQ) three times (at baseline, and then one week and one month later). Reliability and validity of the questionnaires was analysed with Cronbach's alpha and intraclass correlation coefficient. Patients were prospectively followed up for 5 years, with data collected on their use of hospital services and mortality. RESULTS: Cronbach's alpha in the SRI ranged from 0.67 to 0.88 and was >0.7 on all subscales except the "attendant symptoms and sleep". On four subscales, Cronbach's alpha was >0.8, and on the summary scale, 0.95. The SRI showed high correlation with SGRQ. Both tests showed good reproducibility. During the 5-year follow-up, 27 (36%) patients died. CONCLUSIONS: The Finnish SRI proved valid, reliable and reproducible. Its psychometric properties were good and similar to those of the original questionnaire and of other validation studies.

Predictors of New Airway Obstruction - An 11 Year's Population-Based Follow-Up Study.

In the present study we aimed to investigate the incidence and predictors of spirometry based airway obstruction in a representative population-based sample. Altogether 3,863 subjects, 1,651 males and 2,212 females aged ≥30 years had normal spirometry in year 2000. Fifty-three percent of them were never and 23% current smokers. A re-spirometry was performed 11 years later. Several characteristics, such as level of education, use of alcohol, physical activity, diet using Alternate healthy eating (AHEI) index, body mass index, circumwaist, sensitive C reactive protein (CRP) and cotinine of the laboratory values and co-morbidities including asthma, allergic rhinitis, sleep apnoea and chronic bronchitis, as potential risk factors for airway obstruction were evaluated. Using forced expiratory volume in one second/ forced vital capacity below the lower limit of normal, we observed 124 new cases of airway obstruction showing a cumulative 11-year incidence of 3.2% and corresponding to an incidence rate of 5.6/1,000 per year (PY). The incidence rate was higher in men than in women (6.3/1,000 PY vs. 5.0/1,000 PY, respectively). The strongest risk factors were current smoking (Odds ratio [OR] 2.5) and previously diagnosed asthma (OR 2.1). Sensitive CRP associated with the increased risk and high AHEI index with the decreased risk of airway obstruction. Using the similar study approach our findings on the incidence of airway obstruction are in line with the previously published figures in Europe. We were able to confirm the recent findings on the protective effect of healthy diet.

Reference values of inspiratory spirometry for Finnish adults.

Inspiratory spirometry is used in evaluation of upper airway disorders e.g. fixed or variable obstruction. There are, however, very few published data on normal values for inspiratory spirometry. The main aim of this study was to produce reference values for inspiratory spirometry for healthy Finnish adults. Inspiratory spirometry was preplanned to a sample of the Finnish spirometry reference values sample. Data was successfully retrieved from 368 healthy nonsmoking adults (132 males) between 19 and 83 years of age. Reference equations were produced for forced inspiratory vital capacity (FIVC), forced inspiratory volume in one second (FIV1), FIV1/FIVC, peak inspiratory flow (PIF) and the ratios of FIV1/forced expiratory volume in one second and PIF/peak expiratory flow. The present values were compared to PIF values from previously used Finnish study of Viljanen et al. (1982) reference values and Norwegian values for FIV1, FIVC and FIV1/FIVC presented by Gulsvik et al. (2001). The predicted values from the Gulsvik et al. (2001), provided a good fit for FIVC, but smaller values for FIV1 with mean 108.3 and 109.1% of predicted values for males and females, respectively. PIF values were 87.4 and 91.2% of Viljanen et al. (1982) predicted values in males and females, respectively. Differences in measurement methods and selection of results may contribute to the observed differences. Inspiratory spirometry is technically more demanding and needs repeatability criteria to improve validity. New reference values are suggested to clinical use in Finland when assessing inspiratory spirometry. Utility of inspiratory to expiratory values indices in assessment of airway collapse need further study.

Prevalence of life-supporting prolonged invasive ventilation support in Finland.

BACKGROUND: There is no comprehensive data in our country on the prevalence of life-supporting prolonged invasive ventilation support. The objective of the survey was to clarify in all hospital districts of continental Finland the prevalence of patients who were dependent on invasive ventilation support, and the disease leading to the treatment. PATIENTS AND METHODS: The KOTIVEHNO 2015 survey was carried out as population-based cross-sectional study by sending a questionnaire to all doctors in charge of prolonged invasive ventilation support. The questionnaires were used to collect data on the patients within care on 1st January, 2017. RESULTS: The prevalence of life-supporting prolonged invasive ventilation support in Finland among the population aged over 16 years or more was 2/4 patients/100,000 habitants. Altogether 107 patients were within the care. There was variation in the prevalence among the hospital districts. Of the patients, 24% were affected with a motoneuron disease, in 18% the cause was spinal cord injury, 15% suffered from Duchenne's muscular dystrophy, and the rest had some other rare neurological disease. CONCLUSIONS: Life-supporting prolonged invasive ventilation support is rare in Finland. The treatment is associated with neuromuscular diseases causing respiratory insufficiency, and with spinal cord injuries.

Reference values for pulmonary diffusing capacity for adult native Finns.

Measurement standards for pulmonary diffusing capacity were updated in 2005 by the ATS/ERS Task Force. However, in Finland reference values published in 1982 by Viljanen et al. have been used to date. The main aim of this study was to produce updated reference models for single-breath diffusing capacity for carbon monoxide for Finnish adults. Single-breath diffusing capacity for carbon monoxide was measured in 631 healthy non-smoking volunteers (41.5% male). Reference values for diffusing capacity (DLCO), alveolar volume (VA), diffusing capacity per unit of lung volume (DLCO/VA), and lung volumes were calculated using a linear regression model. Previously used Finnish reference values were found to produce too low predicted values, with mean predicted DLCO 111.0 and 104.4%, and DLCO/VA of 103.5 and 102.7% in males and females, respectively. With the European Coalition for Steel and Coal (ECSC) reference values there was a significant sex difference in DLCO/VA with mean predicted 105.4% in males and 92.8% in females (p < .001). New reference values for DLCO, DLCO/VA, VA, vital capacity (VC), inspiratory vital capacity (IVC), and inspiratory capacity (IC) are suggested for clinical use to replace technically outdated reference values for clinical applications.

Prevalence of abnormal findings when adopting new national and international Global Lung Function Initiative reference values for spirometry in the Finnish general population.

BACKGROUND: New Finnish (Kainu2015) and international Global Lung Function Initiative (GLI2012) reference values for spirometry were recently published. The aim of this study is to compare the interpretative consequences of adopting these new reference values with older, currently used Finnish reference values (Viljanen1982) in the general population of native Finns. METHODS: Two Finnish general population samples including 1,328 adults (45% males) aged 21-74 years were evaluated. Airway obstruction was defined as a reduced ratio of forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), possible restrictive pattern as reduced FVC, and decreased ventilatory capacity as reduced FEV1 below their respective 2.5th percentiles. The severity gradings of reduced lung function were also compared. RESULTS: Using the Kainu2015 reference values, the prevalence of airway obstruction in the population was 5.6%; using GLI2012 it was 4.0% and with Viljanen1982 it was 13.0%. Possible restrictive pattern was found in 4.2% using the Kainu2015 values, in 2.0% with GLI2012, and 7.9% with the Viljanen1982 values. The prevalence of decreased ventilatory capacity was 6.8, 4.0, and 13.3% with the Kainu2015, GLI2012 and Viljanen1982 values, respectively. CONCLUSIONS: The application of the GLI2012 reference values underestimates the prevalence of abnormal spirometric findings in native Finns. The adoption of the Kainu2015 reference values reduces the prevalences of airways obstruction, decreased ventilatory capacity, and restrictive impairment by approximately 50%. Changing from the 2.5th percentile, the previously used lower limit of normal, to the 5th percentile recommended by the American Thoracic Society/European Respiratory Society will not increase the prevalence of abnormal findings in the implementation of spirometry reference values.

No change in prevalence of symptoms of COPD between 1996 and 2006 in Finnish adults - a report from the FinEsS Helsinki Study.

BACKGROUND: The age-dependent increase of chronic obstructive pulmonary disease (COPD) prevalence caused by smoking and other inhalational exposures in the general population is well-known worldwide. However, time trends are poorly known, due to lower number of high-quality studies especially following nationwide efforts on diminishing exposure levels. This study aimed to compare the prevalence of COPD symptoms and their major determinants in Finnish adults in 1996 and 2006. METHODS: Two identical postal surveys were conducted among two random population samples from Helsinki using identical methodologies in 1996 and 2006, with 6,062 (76%) and 2,449 (62%) participants, respectively. RESULTS: The physician-diagnoses of COPD remained at 3.7%, whereas physician-diagnoses of asthma and use of asthma medicines increased in both genders. Current smoking reduced from 33.4 to 27.3% (p<0.001), and the amount of cigarettes smoked also reduced significantly. The crude prevalence of chronic productive cough was 12.1 and 11.1%, wheezing with dyspnoea without a cold (wheezing triad) 7.3 and 7.7%, and dyspnoea grade II 13.8 and 13.6%, in 1996 and 2006, respectively. Among subjects with physician-diagnosed COPD, the prevalences of chronic productive cough and recurrent wheeze reduced significantly, from 60.6 to 40.7% and 53.5 to 38.5%, respectively. CONCLUSION: From 1996 to 2006, the prevalence of obstructive airway symptoms common in different phenotypes of COPD did not increase in Finnish adults. This suggests that the upward trend of COPD prevalence might have reached a plateau. Current smoking and the quantities smoked diminished suggesting a wider impact of stronger legislation and smoking-cessation efforts during the Finnish National Programme for COPD.

Respiratory symptoms increase health care consumption and affect everyday life - a cross-sectional population-based study from Finland, Estonia, and Sweden.

BACKGROUND: Even though respiratory symptoms are common in the adult population, there is limited research describing their impact on everyday life and association with health care consumption. AIM: The main objective of this population-based study was to estimate and compare the prevalence of respiratory symptoms among adults in Finland, Estonia, and Sweden in relation to health care consumption and to identify factors influencing health care consumption. A secondary aim was to assess to which extent the presence of respiratory symptoms affect everyday life. METHOD: In the population-based FinEsS studies consisting of random samples of subjects aged 20 to 69 years from Finland (n=1,337), Estonia (n=1,346), and Sweden (n=1,953), data on demographics, respiratory health, and health care consumption were collected by structured interviews. Prevalence was compared and multiple logistic regression analyses were performed. RESULTS: Respiratory symptoms were significantly more common in Finland (66.0%) and Estonia (65.2%) than in Sweden (54.1%). Among subjects with respiratory symptoms, the proportion reporting outpatient care during the past year was fairly similar in the three countries, while specialist consultations were more common in Finland (19.1%), and hospitalisations more common in Estonia (15.0%). Finnish and Estonian residency, female sex, and BMI>25 increased the risk for outpatient care consumption. Wheeze and attacks of shortness of breath in the past 12 months, recurrent sputum production, and cough were associated with an increased risk for health care consumption. Increasing number of respiratory symptoms increased the risk for consuming health care. A larger proportion of subjects in Estonia and Sweden experienced their everyday life being affected by respiratory symptoms compared with subjects in Finland. CONCLUSION: Respiratory symptoms are common in Finland, Estonia, and Sweden and contribute to a negative impact on everyday life as well as increased health care consumption. The observed differences in health care consumption between countries are probably related to national differences in health care structure.

Polynomial estimation of the smoothing splines for the new Finnish reference values for spirometry.

Background Discontinuity of spirometry reference values from childhood into adulthood has been a problem with traditional reference values, thus modern modelling approaches using smoothing spline functions to better depict the transition during growth and ageing have been recently introduced. Following the publication of the new international Global Lung Initiative (GLI2012) reference values also new national Finnish reference values have been calculated using similar GAMLSS-modelling, with spline estimates for mean (Mspline) and standard deviation (Sspline) provided in tables. The aim of this study was to produce polynomial estimates for these spline functions to use in lieu of lookup tables and to assess their validity in the reference population of healthy non-smokers. Methods Linear regression modelling was used to approximate the estimated values for Mspline and Sspline using similar polynomial functions as in the international GLI2012 reference values. Estimated values were compared to original calculations in absolute values, the derived predicted mean and individually calculated z-scores using both values. Results Polynomial functions were estimated for all 10 spirometry variables. The agreement between original lookup table-produced values and polynomial estimates was very good, with no significant differences found. The variation slightly increased in larger predicted volumes, but a range of -0.018 to +0.022 litres of FEV1 representing ± 0.4% of maximum difference in predicted mean. Conclusions Polynomial approximations were very close to the original lookup tables and are recommended for use in clinical practice to facilitate the use of new reference values.

GOLD criteria overestimate airflow limitation in one-third of cases in the general Finnish population.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) diagnostic criteria for chronic obstructive pulmonary disease (COPD) use a fixed threshold of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio (<0.70) in post-bronchodilation spirometry to indicate disease, which has been shown to underestimate and overestimate disease prevalence in younger and older adults, respectively, whilst criteria based on reference values have better accuracy. Differences in reference values have limited their use in international studies. However, the new Global Lung Function Initiative reference values (GLI2012) showed FEV1/FVC to be the least dependent on ethnicity. The aim of this study was to assess the prevalence of airflow limitation with GLI2012 and the degree of underdetection or overestimation related to the use of GOLD in the general population. A Finnish population sample of 1323 subjects (45% male) with post-bronchodilation spirometry was studied. 80 subjects (6.0%) and 55 subjects (4.2%) were identified with airflow limitation with GOLD and GLI2012 criteria, respectively. The proportion of overestimation with GOLD increased with age from 25% of cases in 50-year-olds to 54% in 70-year-olds. Using z-score-based grading resulted in more dispersion in severity grading. In conclusion, the GOLD criteria cause a marked overestimation already from 50-year-olds and should be replaced with the GLI2012 criteria to improve diagnostic accuracy.

Reference values for spirometry - report from the Obstructive Lung Disease in Northern Sweden studies.

BACKGROUND: Abnormal lung function is commonly identified by comparing observed spirometric values to corresponding reference values. It is recommended that such reference values for spirometry are evaluated and updated frequently. The aim of this study was to estimate new reference values for Swedish adults by fitting a multivariable regression model to a healthy non-smoking general population sample from northern Sweden. Further aims were to evaluate the external validity of the obtained reference values on a contemporary sample from south-western Sweden, and to compare them to the Global Lung Function Initiative (GLI) reference values. METHOD: Sex-specific multivariable linear regression models were fitted to the spirometric data of n=501 healthy non-smoking adults aged 22-91 years, with age and height as predictors. The models were extended to allow the scatter around the outcome variable to depend on age, and age-dependent spline functions were incorporated into the models to provide a smooth fit over the entire age range. Mean values and lower limits of normal, defined as the lower 5th percentiles, were derived. RESULT: This modelling approach resulted in unbiased estimates of the spirometric outcomes, and the obtained estimates were appropriate not only for the northern Sweden sample but also for the south-western Sweden sample. On average, the GLI reference values for forced expiratory volume in one second (FEV1) and, in particular, forced expiratory vital capacity (FVC) were lower than both the observed values and the new reference values, but higher for the FEV1/FVC ratio. CONCLUSION: The evaluation based on the sample of healthy non-smokers from northern Sweden show that the Obstructive Lung Disease in Northern Sweden reference values are valid. Furthermore, the evaluation based on the south-western Sweden sample indicates a high external validity. The comparison with GLI brought further evidence to the consensus that, when available, appropriate local population-specific reference values may be preferred.

High prevalence of rhinitis symptoms without allergic sensitization in Estonia and Finland.

OBJECTIVES: Allergic rhinitis and atopy are more common in urban than rural environments. Non-allergic rhinitis has not been studied to a great extent. We aimed to assess the relationship of rhinitis symptoms with different profiles of allergic sensitization, comparing this in rural and urban environments. METHODS: The study population consisted of population-based cohorts of adults aged 26-60 from Helsinki, Finland, and rural Saaremaa and urban Tallinn, Estonia. We compared the results of a structured interview and skin prick tests and assessed the risk factors for rhinitis. RESULTS: The prevalence of rhinitis symptoms with atopy was 32.7% in Helsinki, 20.8% in Tallinn, and 12.5% in Saaremaa (p<0.001). Rhinitis symptoms without atopy were found in 26.4%, 29.8%, and 29.3% (p=n.s.), respectively. In Helsinki, 87.3% of participants with atopy identified symptoms as allergic, compared to 57.0% in Tallinn and 47.5% in Saaremaa. Childhood in the countryside (OR 0.63), family history of allergic rhinitis (OR 1.89), and polysensitization (OR 15.99) were significantly associated with rhinitis symptoms with atopy in a multivariate logistic regression model. The most common sensitizers were pollens and animals in Helsinki and mites in Estonia. Exposure to environmental tobacco smoke (OR 1.50) and family history of allergic rhinitis (OR 1.70) were associated with rhinitis symptoms without atopy. CONCLUSION: Rhinitis symptoms without allergic sensitization were common in both Finland and Estonia and were associated with environmental tobacco smoke. Family history of allergic rhinitis predisposed to rhinitis symptoms irrespective of atopy status.

Combined effect of smoking and occupational exposure to dusts, gases or fumes on the incidence of COPD.

To assess risk factors related to the development of chronic obstructive pulmonary disease (COPD) including smoking and occupational exposure (OE) to dusts, gases or fumes, we performed a longitudinal 11-year follow-up postal survey. The original study population was a random population sample of 8000 inhabitants of Helsinki aged 20 to 69 years in 1996. Participants of the first postal questionnaire were invited to this follow-up survey in 2007 with 4302 (78%) answers obtained. Cumulative incidence of COPD in 11 years was 3.43% corresponding to an incidence rate of 3.17/1000/year after exclusion of those with self-reported physician-diagnosed COPD and ever COPD in 1996. Smoking and age, but not gender, were associated with incident COPD. Reported family history of COPD increased the cumulative incidence to 8.55% vs 3.04% among those without a family history (p < 0.001). In multivariate analysis, significant independent risk factors for incident COPD were: current smoking in 1996 (OR 4.40 [95% CI 2.89-6.71]), age over 50 (OR 3.42 [95% CI 2.22-5.26]), family history of COPD (OR 2.08 [1.27-3.43]), ever asthma (OR 2.28 [1.35-3.86]), and self-reported OE (OR 2.14 [1.50-3.05]). Occupational exposure to dusts, gases or fumes, assessed both based on self-reported exposure and a job exposure matrix using reported professions, was an independent risk factor for incident COPD. Smoking and OE together yielded an additive effect on incidence of COPD.

COPD in Helsinki, Finland: socioeconomic status based on occupation has an important impact on prevalence.

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is globally a major, but often undiagnosed, cause of morbidity and mortality. The aims of this study were to assess the prevalence of COPD in Helsinki, Finland, with international diagnostic criteria and to analyse risk factors including socioeconomic status, and disease severity. METHODS: A general population sample of 628 adults (368 women) completed flow-volume spirometry with bronchodilation test and a structured interview. Post-bronchodilation spirometry was assessed both using the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria and relative to the fifth percentile of the reference value (lower limit of normal, LLN). RESULTS: According to GOLD criteria, 37 (5.9%), and by using the LLN criteria, 43 subjects (6.8%) had airway obstruction consistent with COPD. Using the GOLD criteria, four subjects or 0.6% of the population had severe, 3.0% moderate, and 2.2% mild COPD. Of those with post-bronchodilator obstruction, 49% had no previous diagnosis of obstructive airways disease and did not use medication for any respiratory disease. The prevalence of undiagnosed COPD defined by GOLD was 2.9% (LLN 3.3%). In addition to age, smoking history, and prior history of asthma, socioeconomic status based on occupation was significantly related to COPD in the population. Manual workers in industry (GOLD 10.0%, LLN 11.7%) and non-manual assistant employees (10.2%, 10.2%) had a significantly higher prevalence of COPD than professionals (2.8%, 2.3%). CONCLUSIONS: Although smoking is the main modifiable risk factor for COPD, the disease was significantly related to manual workers and non-manual assistant employees, i.e. socioeconomic groups reflecting occupation.

Increase in prevalence of physician-diagnosed asthma in Helsinki during the Finnish Asthma Programme: improved recognition of asthma in primary care? A cross-sectional cohort study.

BACKGROUND: The continuing rise in asthma prevalence has been questioned, with recent reports suggesting a plateau. AIMS: To assess a 10-year trend in the age-adjusted prevalence of physician-diagnosed asthma, respiratory and allergic symptoms, and use of asthma medication in the adult population of Helsinki during the Finnish Asthma Programme from 1994 to 2004. METHODS: Two cross-sectional postal surveys were conducted among random Finnish National Population Registry samples 10 years apart using the same protocol. A total of 6,062 subjects (75.9%) and 2,449 subjects (61.9%) participated in 1996 and 2006, respectively. RESULTS: The prevalence of physician-diagnosed asthma increased from 6.5% in 1996 to 10.0% in 2006 (p<0.001). This was evident in both genders aged <60 years, but particularly in women aged <40 years, paralleling an increased use of asthma medication. Concurrently, the prevalence of allergic rhinoconjunctivitis increased from 37.2% to 44.4% (p<0.001). The prevalence of physician-diagnosed chronic obstructive pulmonary disease remained unchanged (3.7%), while current smoking abated. Subjects with a smoking history had more respiratory symptoms (p<0.001). Among subjects without physician-diagnosed asthma, those reporting allergic rhinoconjunctivitis had a higher prevalence of lower respiratory tract symptoms. CONCLUSIONS: The prevalence of allergic rhinoconjunctivitis and physician-diagnosed asthma has increased in Helsinki during 10 years in adults, especially in women aged <40 years. Concomitantly, the use of asthma medication increased and subjects with physiciandiagnosed asthma were less symptomatic. The increase in the prevalence of physician-diagnosed asthma may partly be due to improved diagnostic recognition of asthma in primary care during the Finnish Asthma Programme, but the concurrent rise in allergic rhinoconjunctivitis may reflect a true rise in prevalence.

Reduction of fractional exhaled nitric oxide (FENO) and its variation by mouth wash.

INTRODUCTION: Although fractional exhaled nitric oxide (FENO) measurement is a widely used method to assess eosinophilic bronchial inflammation, knowledge on extrabronchial factors affecting measurement results is still limited. Our aim was to study the eventual modifying effect of mouth wash on FENO values and their variability. MATERIALS AND METHODS: A total of 16 healthy Caucasian women performed FENO measurements with a chemiluminescence analyzer according to ATS guidelines (2005), with an exhalation flow rate of 50 ml/s against a flow resistor. On the first day three successive FENO measurements were performed: first after mouth wash with water containing sodium and potassium bicarbonates, and thereafter twice without mouth wash. On the second day, the FENO measurement was first performed without mouth wash, then with preceding mouth wash twice, and finally without preceding mouth wash. Each FENO measurement consisted of three measurements with the average reported and the time interval between the FENO measurements was 10 minutes on both days. RESULTS: The FENO level increased significantly in the subsequent measurements performed without mouth wash (p < 0.01), when the baseline measurement was performed with mouth wash. On the second day, the FENO level decreased significantly in measurements performed with preceding mouth wash, compared with the first measurement without preceding mouth wash (p < 0.01). CONCLUSION: The results indicate a slight but statistically significant decreasing effect of mouth wash on the FENO. The findings suggest that mouth wash prior to FENO measurement could standardize the measurement procedure, by decreasing the effect of NO produced in the mouth on the measurement result.

Repeatability of exhaled nitric oxide measurements in patients with COPD.

The assessment of the presence of eosinophilic airway inflammation may help in predicting the steroid response in subjects with respiratory symptoms. Unlike patients with asthma, only a subset of patients with chronic obstructive pulmonary disease (COPD) benefits from steroid treatment. Fractional exhaled nitric oxide (FENO) is a useful surrogate marker for eosinophilic airway inflammation, but data on the repeatability of FENO measurements in COPD needed for the assessment of significant change are insufficient. The aim of this study was to assess the short-term repeatability of FENO measurement in subjects with moderate to very severe chronic airway obstruction compared to that in healthy subjects. We studied 20 patients with stable COPD and 20 healthy subjects, and determined FENO (flow rate 50 ml s(-1) ) three times: at baseline, 10 min and 24 h after baseline. Spirometry was performed on the first study day after the FENO measurements. The median FENO concentration in patients with COPD was 15·6 ppb, and in healthy subjects, 15·2 ppb. The coefficient of variation (CoV) for 24-h measurements was 12·4% in COPD patients, and 15·9% in healthy subjects. Among COPD patients with global initiative for chronic obstructive lung disease stage 2 disease, the CoV was 13·7%, and among those with stage 3-4 disease, 10·5%. The findings indicate that the short-term repeatability of FENO measurement in patients with moderate to very severe COPD is equally good as in healthy subjects. A change in FENO exceeding 24% is likely to reflect a minimum measurable change in COPD.

Responses of FEV6, FVC, and FET to inhaled bronchodilator in the adult general population.

BACKGROUND: The assessment of bronchodilator-induced change in forced vital capacity (FVC) is dependent on forced expiratory time (FET) in subjects with airflow limitation. Limited information is available on the concurrent responses of FVC, forced expiratory volume in six seconds (FEV6), and FET in the bronchodilation test among patients with obstructive airways disease or in the general population. The aim of this study was to assess the changes in FEV6, FVC, and FET, and their relationships in a standardized bronchodilation test in the general population. METHODS: We studied bronchodilation response in a general adult population sample of 628 individuals (260 men, 368 women) with flow-volume spirometry. The largest FVC, the corresponding FET and the largest FEV6 both at the baseline and after 0.4 mg of inhaled salbutamol were selected for analysis. RESULTS: After administration of salbutamol FEV6 decreased on average -13.4 (95% CI -22.3 to -4.5) ml or -0.2% (-0.4% to 0.0%) from the baseline. The 95th percentile of change in FEV6 was 169.1 ml and 5.0%. FVC decreased on average -42.8 (-52.4 to -33.3) ml or -1.0% (-1.2% to -0.7%). Concurrently FET changed on average -0.2 (-0.4 to 0.0) seconds or 0.4% (-1.4% to 2.3%). There were four subjects with an increase of FVC over 12% and only one of these was associated with prolonged FET after salbutamol. Changes in FEV6 and FVC were more frequently positive in subjects with reduced FEV1/FVC in baseline spirometry. CONCLUSION: In general adult population, both FEV6 and FVC tended to decrease, but FET remained almost unchanged, in the bronchodilation test. However, those subjects with signs of airflow limitation at the baseline showed frequently some increase of FEV6 and FVC in the bronchodilation test without change in FET. We suggest that FEV6 could be used in assessment of bronchodilation response in lieu of FVC removing the need for regulation of FET during bronchodilation testing.

FEV1 response to bronchodilation in an adult urban population.

BACKGROUND: Most studies evaluating bronchodilation in flow-volume spirometry have been conducted in patients with obstructive airways diseases, but less is known about bronchodilation responses in the general population or in healthy subjects. METHODS: We evaluated an urban population sample of 628 adults (260 men, 368 women) aged 25 to 74 years with flow-volume spirometry using inhalation of 0.4 mg of a salbutamol aerosol with a spacer device for bronchodilation. On the basis of a structured interview, a subgroup of 219 healthy, asymptomatic nonsmokers was selected. RESULTS: In the population sample, the average increase in FEV(1) from baseline after salbutamol inhalation was 77.2 mL (SD, 109.7 mL) or 2.5% (SD, 3.9%). In healthy asymptomatic nonsmokers, the mean change in FEV(1) was 62.0 mL (SD, 89.7 mL) or 1.8% (SD, 2.6%). In the whole population, the 95th percentile limit of the increase in FEV(1) was 8.5%, while it was 5.9% among healthy asymptomatic nonsmokers. The absolute change in FEV(1) correlated significantly with baseline FVC (p < 0.01). The FEV(1)/FVC ratio at baseline was the strongest influencing factor for the bronchodilation response. CONCLUSIONS: The results indicate that a significant increase in FEV(1) from baseline in a bronchodilation test is around 9% in an urban population. The level of the significant absolute increase in FEV(1) seems to depend on FVC. Low baseline FEV(1)/FVC ratio, reflecting airflow limitation, is the strongest determinant for FEV(1) response to bronchodilation.