Parallel gradients in FENO and in the prevalences of asthma and atopy in adult general populations of Sweden, Finland and Estonia - A Nordic EpiLung study.

The prevalence of asthma is higher in Sweden and Finland than in neighbouring eastern countries including Estonia. Corresponding difference in bronchial eosinophilic inflammation could be studied by FENO measurements. We aimed to compare FENO in adult general populations of Sweden, Finland, and Estonia, to test the plausibility of the west-east disparity hypothesis of allergic diseases. We conducted clinical interviews (N = 2658) with participants randomly selected from the general populations in Sweden (Stockholm and Örebro), Finland (Helsinki), and Estonia (Narva and Saaremaa), and performed FENO (n = 1498) and skin prick tests (SPT) in 1997-2003. The median (interquartile range) of FENO (ppb) was 15.5 (9.3) in Sweden, 15.4 (13.6) in Finland and 12.5 (9.6) in Estonia. We found the lowest median FENO values in the Estonian centres Saaremaa 13.1 (9.5) and Narva 11.8 (8.6). In the pooled population, asthma was associated with FENO ≥25 ppb, odds ratio (OR) 3.91 (95% confidence intervals: 2.29-6.32) after adjusting for SPT result, smoking, gender and study centre. A positive SPT test increased the likelihood of asthma OR 3.19 (2.02-5.11). Compared to Saaremaa, the likelihood of having asthma was higher in Helsinki OR 2.40 (1.04-6.02), Narva OR 2.45 (1.05-6.19), Örebro OR 3.38 (1.59-8.09), and Stockholm OR 5.54 (2.18-14.79). There was a higher prevalence of asthma and allergic airway inflammation in adult general populations of Sweden and Finland compared to those of Estonia. Atopy and elevated FENO level were independently associated with an increased risk of asthma. In conclusion, the findings support the earlier west-east disparity hypothesis of allergic diseases.

[Endobronchial ultrasonography--when needed?]. / Keuhkoputkien kaikutähystys--milloin tarpeen?

Endobronchial ultrasonography (EBUS) and associated needle biopsy is a mini-invasive means to study mediastinal and hilar lymph nodes and tumors. Guidance by real-time ultrasound image allows the biopsy of even small targets with high accuracy. The investigation is well tolerated, highly specific and its main indication is the staging of lung cancer. The method is also suitable for primary diagnosis of mediastinal lymphadenopathy of unknown origin or central tumors.

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.

[Smoking and drug interactions]. / Tupakointi ja lääkeinteraktiot.

Smoking causes certain clinically significant drug interactions. Polycyclic aromatic hydrocarbons induce CYP1A2 enzyme, which is important in metabolism of several drugs. This enzyme induction can lead todecreased efficacy of certain psychoactive drugs, teophylline, warfarin, certain antiarythmicsand anticancer drugs. In addition, nicotine may interfere with the action of beta-blockers and benzodiatsepines through pharmacodynamic mechanisms. After smoking cessation the induced metabolism begins to normalize increasing the risks related to elevated drug concentrations. The risk is highestwhen using drugs with narrow therapeutic ratio, such as clozapine and theophylline. Compared to enzyme inhibition, enzyme-induction takes significantly longer to develop and longer to normalize after abolition of the enzyme inductor. When planning smoking cessation or when a smoker is acutely hospitalized, the medication has to be screened and need for changes in dosages and measurements of drug concentrations to be evaluated.

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.

Smoking attenuates increase in exhaled nitric oxide in atopic but not in nonatopic young adults with asthma.

BACKGROUND: Measurement of fractional exhaled nitric oxide (FENO) is useful in assessing eosinophilic airway inflammation. Smoking may modify airway inflammation and reduce FENO levels, compromising the diagnostic value of FENO in smokers. How smoking influences FENO in atopic versus nonatopic asthmatics is unknown. The aim of the present study was to compare FENO in atopic and nonatopic steroid-naive young asthmatic adults and in healthy subjects in terms of smoking. METHODS: Forty-six (30 atopic) smoking and 70 (54 atopic) nonsmoking steroid-naive army conscripts (mean age 20 years) with current symptomatic asthma underwent FENO measurement, skin prick tests, spirometry with a bronchodilation test, bronchial histamine challenge, and a standardized exercise test. Ten healthy smokers and 9 healthy nonsmokers underwent FENO measurement, spirometry and bronchial histamine challenge. RESULTS: Smokers with asthma showed significantly higher FENO than did healthy smokers and nonsmokers (p = 0.001, both comparisons). Among atopic asthmatics, FENO was lower in smokers than in nonsmokers (p = 0.002) whereas among nonatopic asthmatics no such difference was detectable (p = 0.89). However, even among nonatopic asthmatic smokers FENO was significantly higher than among healthy controls (p = 0.01). CONCLUSION: Smoking seems to attenuate the increase in FENO in atopic but not in nonatopic asthmatics. This finding suggests differences in biochemical mechanisms of NO formation in atopic and nonatopic asthma. However, FENO was significantly higher both in atopic and nonatopic asthmatic smokers than in healthy controls. This suggests that FENO can be applied for diagnostic purposes also in young adult smokers.

[Bevacizumab in the treatment of non-small cell lung cancer]. / Bevasitsumabi ei-pienisoluisen keuhkosyövän hoidossa.

Treatment of advanced or metastatic non-small cell lung cancer with current cytotoxic agents is at its best able to only slow down the progression of the disease, while no curative treatment is known. Novel antiangiogenetic agents such as Bevacizumab have been expected to bring about a change in the treatment and prognosis of this disease. Two randomized studies have been conducted with Bevacizumab, whereby it was observed to make the therapeutic results more effective when combined with a cytotoxic platinum agent in a selected patient group. In our opinion the current scientific evidence does not yet support the use of Bevacizumab as the standard therapy for lung cancer.

Equally elevated concentrations of exhaled nitric oxide in nonatopic and low-sensitized atopic asthmatics.

BACKGROUND: Some studies show concentrations of exhaled nitric oxide (FENO) in nonatopic asthma and in healthy subjects to be similar, but include asthmatics on inhaled steroids, which is likely to interfere with the results. AIM: Comparison of FENO between nonatopic asthmatics, low-sensitized and high-sensitized atopic asthmatics, and healthy controls. METHODS: We studied 85 non-smoking, steroid-naive young men with recently diagnosed symptomatic asthma and 10 healthy controls. FENO was measured according to European Respiratory Society Guidelines. In skin prick tests of 13 common aeroallergens, subjects with a total sum of prick wheals 3-10mm were regarded as low-sensitized and those with >10mm, as high-sensitized. Flow-volume spirometry, standardized histamine challenge, and an exercise test were also carried out. RESULTS: Prick tests revealed 14 subjects to be nonatopic and 71 atopic. In high-sensitized subjects with atopic asthma, the FENO median (25-75 quartiles) was significantly higher, 34.9 (21.3-53.8) parts per billion (ppb), than in subjects with nonatopic asthma, 15.2 (9.7-24.7)ppb (p<0.001), both being significantly higher than in healthy controls, 6.6 (5.2-8.5)ppb (p<0.001). FENO levels were similar in nonatopic and in low-sensitized atopic asthmatics, with no difference between them in bronchial responsiveness to histamine and exercise. CONCLUSION: Among steroid-naive young male asthmatics, FENO was equally elevated in nonatopic asthma and in low-sensitized atopic asthma but lower than in those with high-sensitized atopic asthma. These differences in FENO between asthma groups parallel the differences in airway function disturbance in terms of responsiveness to histamine or exercise.

Atopic sensitization to common allergens without symptoms or signs of airway disorders does not increase exhaled nitric oxide.

BACKGROUND: Elevated fractional exhaled nitric oxide (FENO) associates positively with symptomatic atopy among asthmatics and in the general population. It is, however, unclear whether sensitization to common allergens per se- as verified with positive skin prick tests--affects FENO in healthy individuals. OBJECTIVE: The aim of this study was to examine the association between FENO and sensitization to common allergens in healthy nonsmoking adults with no signs or symptoms of airway disorders. METHODS: FENO measurements (flow rate: 50 mL/s), skin prick tests to common inhalant allergens, structured interviews, spirometry, bronchodilatation tests and bronchial histamine challenges were performed on a randomly selected population of 248 subjects. Seventy-three of them (29%) were nonsmoking asymptomatic adults with no history of asthma, persistent or recurrent upper or lower airway symptoms and no signs of airway disorders in the tests listed above. RESULTS: FENO concentrations were similar in skin prick test positive (n = 32) and negative (n = 41) healthy subjects, with median values of 13.2 and 15.5 ppb, respectively (P = 0.304). No correlation appeared between FENO and the number of positive reactions (r = -0.138; P = 0.244), or the total sum of wheal diameters (r = -0.135; P = 0.254). The nonparametric one-tailed 95% upper limits of FENO among skin prick positive and negative healthy nonsmoking subjects were 29 and 31 ppb, respectively. CONCLUSIONS: Atopic constitution defined as positive skin prick test results does not increase FENO in healthy nonsmoking adults with no signs or symptoms of airway disorders. This suggests that same reference ranges for FENO can be applied to both skin prick test positive and negative subjects.

Increased oxidative stress in asymptomatic current chronic smokers and GOLD stage 0 COPD.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with increased oxidative and nitrosative stress. The aim of our study was to assess the importance of these factors in the airways of healthy smokers and symptomatic smokers without airway obstruction, i.e. individuals with GOLD stage 0 COPD. METHODS: Exhaled NO (FENO) and induced sputum samples were collected from 22 current smokers (13 healthy smokers without any respiratory symptoms and 9 with symptoms i.e. stage 0 COPD) and 22 healthy age-matched non-smokers (11 never smokers and 11 ex-smokers). Sputum cell differential counts, and expressions of inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE) were analysed from cytospins by immunocytochemistry. Eosinophil cationic protein (ECP) and lactoferrin were measured from sputum supernatants by ELISA. RESULTS: FENO was significantly decreased in smokers, mean (SD) 11.0 (6.7) ppb, compared to non-smokers, 22.9 (10.0), p < 0.0001. Induced sputum showed increased levels of neutrophils (p = 0.01) and elevated numbers of iNOS (p = 0.004), MPO (p = 0.003), nitrotyrosine (p = 0.003), and 4-HNE (p = 0.03) positive cells in smokers when compared to non-smokers. Sputum lactoferrin levels were also higher in smokers than in non-smokers (p = 0.02). Furthermore, we noted four negative correlations between FENO and 1) total neutrophils (r = -0.367, p = 0.02), 2) positive cells for iNOS (r = -0.503, p = 0.005), 3) MPO (r = -0.547, p = 0.008), and 4) nitrotyrosine (r = -0.424, p = 0.03). However, no major differences were found between never smokers and ex-smokers or between healthy smokers and stage 0 COPD patients. CONCLUSION: Our results clearly indicate that several markers of oxidative/nitrosative stress are increased in current cigarette smokers compared to non-smokers and no major differences can be observed in these biomarkers between non-symptomatic smokers and subjects with GOLD stage 0 COPD.