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.

Measurement of bronchial hyperreactivity: comparison of three Nordic dosimetric methods.

Clinical testing of bronchial hyperreactivity (BHR) provides valuable information in asthma diagnostics. Nevertheless, the test results depend to a great extent on the testing procedure: test substance, apparatus and protocol. In Nordic countries, three protocols predominate in the testing field: Per Malmberg, Nieminen and Sovijärvi methods. However, knowledge of their equivalence is limited. We aimed to find equivalent provocative doses (PD) to obtain similar bronchoconstrictive responses for the three protocols. We recruited 31 patients with suspected asthma and health care workers and performed BHR testing with methacholine according to Malmberg and Nieminen methods, and with histamine according to Sovijärvi. We obtained the individual response-dose slopes for each method and predicted equivalent PD values. Applying a mixed-model, we found significant differences in the mean (standard error of mean) response-dose (forced expiratory volume in one second (FEV1)%/mg): Sovijärvi 7.2 (1.5), Nieminen 13.8 (4.2) and Malmberg 26 (7.3). We found that the earlier reported cut-point values for moderate BHR and marked BHR between the Sovijärvi (PD15) and Nieminen (PD20) methods were similar, but with the Malmberg method a significant bronchoconstrictive reaction was measured with lower PD20 values. We obtained a relationship between slope values and PD (mg) between different methods, useful in epidemiological research and clinical practice.

Converting FENO by different flows to standard flow FENO.

In clinical practice, assessment of expiratory nitric oxide (FENO ) may reveal eosinophilic airway inflammation in asthmatic and other pulmonary diseases. Currently, measuring of FENO is standardized to exhaled flow level of 50 ml s-1 , since the expiratory flow rate affects the FENO results. To enable the comparison of FENO measured with different expiratory flows, we firstly aimed to establish a conversion model to estimate FENO at the standard flow level, and secondly, validate it in five external populations. FENO measurements were obtained from 30 volunteers (mixed adult population) at the following multiple expiratory flow rates: 50, 30, 100 and 300 ml s-1 , after different mouthwash settings, and a conversion model was developed. We tested the conversion model in five populations: healthy adults, healthy children, and patients with COPD, asthma and alveolitis. FENO conversions in the mixed adult population, in healthy adults and in children, showed the lowest deviation between estimated F ^ ENO from 100 ml s-1 and measured FENO at 50 mL s-1 : -0·28 ppb, -0·44 ppb and 0·27 ppb, respectively. In patients with COPD, asthma and alveolitis, the deviation was -1·16 ppb, -1·68 ppb and 1·47 ppb, respectively. We proposed a valid model to convert FENO in healthy or mixed populations, as well as in subjects with obstructive pulmonary diseases and found it suitable for converting FENO measured with different expiratory flows to the standard flow in large epidemiological data, but not on individual level. In conclusion, a model to convert FENO from different flows to the standard flow was established and validated.

Vasomotor hot flashes and cardiac repolarization: a randomized placebo-controlled trial of postmenopausal hormone therapy.

OBJECTIVE: The aim of the study was to compare the effects of different hormone therapies on cardiac repolarization in recently postmenopausal women with and without hot flashes. METHODS: We recruited 150 healthy women: 72 with and 78 without hot flashes. They were randomized and treated for 6 months with transdermal estradiol (1 mg/day), oral estradiol (OE) alone (2 mg/day) or combined with medroxyprogesterone acetate (MPA; 5 mg/day), or placebo. Cardiac repolarization was assessed by measuring QT intervals, rate-dependence of QT-end interval, and T waves from 24-hour electrocardiographic recording before and during hormone therapy, comprising a total of over 20 million QT-interval measurements. RESULTS: Hot flashes were accompanied with shortened median T-peak - T-end interval (at RR interval of 700, 800, and 900 ms; P = 0.040, 0.020, and 0.032; η = 0.35, 0.39, and 0.37; respectively) during the use of OE but not transdermal estradiol. In contrast, the addition of MPA to OE lengthened the maximal QT-end (at RR interval of 500 ms, P = 0.016, η = 0.27) and the maximal T-peak - T-end interval (at RR interval of 500 and 600 ms; P = 0.016 and 0.032; η = 0.25 and 0.22, respectively). These effects were not seen in women without hot flashes. CONCLUSIONS: Hot flashes predict beneficial shortening in cardiac repolarization during OE, but not if MPA is combined with OE. These data may provide one explanation for MPA-related cardiac hazards in epidemiological studies.

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.

Cardiac repolarization in recently postmenopausal women with or without hot flushes.

OBJECTIVE: Menopausal hot flushes are associated with elevated activity of the sympathetic nervous system and may be related to increased risk for cardiovascular events. Sympathetic activation may trigger severe arrhythmias by modulating cardiac repolarization. The aim of this study was to evaluate the impact of hot flushes on cardiac repolarization in postmenopausal women with and without hot flushes. METHODS: We assessed 150 recently postmenopausal healthy women-72 with hot flushes and 78 without hot flushes. They underwent 24-hour electrocardiographic recording, comprising a total of over 10,000,000 QT-interval measurements. The cardiac repolarization was assessed by measuring QT-intervals, heat rate dependence of QT-end intervals, and T-waves. RESULTS: The maximal QT-end interval was shorter in women with hot flushes compared with those without hot flushes (481 ±â€Š64 ms vs 493 ±â€Š50 ms; P = 0.046). There were no differences between the rate dependence of QT-end intervals and T-wave measures between the groups. During the night-time hot flush period, we detected a steeper rate-dependence of QT-end intervals and a longer maximal T-peak-T-end interval (117 ±â€Š54 ms vs 111 ±â€Š56 ms; P < 0.001) compared with the control period. CONCLUSIONS: Women with hot flushes did not have clinically significant differences in ambulatory cardiac repolarization measurements compared with asymptomatic women. However, a sudden sympathetic surge occurring during the night-time hot flush may have direct effects on cardiac repolarization.

Thoracic gas compression during forced expiration in patients with emphysema, interstitial lung disease and obesity.

BACKGROUND: Dynamic gas compression during forced expiration has an influence on conventional flow-volume spirometry results. The extent of gas compression in different pulmonary disorders remains obscure. Utilizing a flow plethysmograph we determined the difference between thoracic and mouth flows during forced expiration as an indication of thoracic gas compression in subjects with different pulmonary diseases characterized by limitations in pulmonary mechanics. METHODS: Patients with emphysema (N = 16), interstitial lung disease (ILD) (N = 15), obesity (N = 15) and healthy controls (N = 16) were included. Compressed expiratory flow-volume curves (at mouth) and corresponding compression-free curves (thoracic) were recorded. Peak flow (PEF) and maximal flows at 75%, 50% and 25% of remaining forced vital capacity (MEF75, MEF50 and MEF25) were derived from both recordings. Their respective difference was assessed as an indicator of gas compression. RESULTS: In all groups, significant differences between thoracic and mouth flows were found at MEF50 (p < 0.01). In controls, a significant difference was also measured at MEF75 (p <0.005), in emphysema subjects, at PEF and MEF75 (p < 0.05, p < 0.005) and in obese subjects at MEF75 (p <0.005) and MEF25 (p < 0.01). ILD patients showed the lowest difference between thoracic and mouth flows at MEF75 relative to controls and emphysema patients (p < 0.005, p < 0.001). Obese subjects did not differ from controls, however, the difference between thoracic and mouth flows was significantly higher than in patients with emphysema at MEF50 (p < 0.001) and MEF25 (p < 0.005). CONCLUSIONS: Alveolar gas compression distorts the forced expiratory flow volume curve in all studied groups at the middle fraction of forced expiratory flow. Consequently, mouth flows are underestimated and the reduction of flow measured at 75% and 50% of vital capacity is often considerable. However, gas compression profiles in stiff lungs, in patients with decreased elastic recoil in emphysema and in obesity differ; the difference between thoracic and mouth flows in forced expiration was minimal in ILD at the first part of forced expiration and was higher in obesity than in emphysema at the middle and last parts of forced expiration.

[Spiroergometry in the assessment of exercise capacity and associated restrictive factors]. / Spiroergometria fyysisen suorituskyvyn ja sitä rajoittavien tekijöiden arvioinnissa.

Compared with the conventional clinical exercise test, spiroergometry can provide a more accurate means of finding out the causes of restricted exercise capacity. Result profiles of spiroergometric parameters yield information about the pathophysiologic mechanisms of various disease conditions. The investigation is most commonly carried out to find out whether the fatigue or dyspnea restricting the exercise capacity is due to functional disturbances of the heart or the lungs, or perhaps to myogenic causes. Parameters measuring gas exchange and pulmonary ventilation yield a picture of the mechanics of breathing and its disturbances, and indirectly reveal the onset of blood lactate accumulation during exercise.

Menopausal hot flushes do not associate with changes in heart rate variability in controlled testing: a randomized trial on hormone therapy.

OBJECTIVE: To compare in controlled cardiovascular autonomic function tests the effects of hormone therapy (HT) on heart rate variability (HRV) responses in postmenopausal women with and without pretreatment hot flushes. DESIGN: A randomized placebo-controlled trial. SETTING: Finland, Helsinki University Central Hospital. POPULATION: A total of 150 recently postmenopausal and healthy women with prospectively evaluated hot flushes. METHODS: Women (72 with and 78 without hot flushes) were randomized to receive estradiol alone or in combination with medroxyprogesterone acetate or placebo for 6 months. Time and frequency domain measures of HRV were assessed at baseline and after HT with short-term recordings during paced quiet and deep breathing and with active orthostatic tests, both under carefully controlled laboratory conditions to avoid confounding factors present in long-term ambulatory HRV measurements. MAIN OUTCOME MEASURES: Responses of time and frequency domain measures of HRV to HT. RESULTS: At baseline HRV was similar in women with and without hot flushes. Pretreatment hot flushes did not associate with changes in time domain parameters of HRV during controlled quiet or deep breathing or active orthostatic tests after different types of HT. However, HT reduced HRV in very low frequency power in women with pretreatment hot flushes (from 371 ± 40 to 258 ± 28 ms(2) , p = 0.018). HT did not have an effect on other frequency domain measures during quiet breathing or active orthostatic tests. CONCLUSIONS: Hormone therapy did not significantly modify the HRV responses in women with or without hot flushes under controlled short-term measurements of the cardiovascular autonomic nervous system.

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.

Vasomotor hot flashes and heart rate variability: a placebo-controlled trial of postmenopausal hormone therapy.

OBJECTIVE: The aim of the study was to compare the responses of heart rate variability (HRV) with hormone therapy in recently postmenopausal women with and without vasomotor hot flashes. METHODS: Seventy-two women with and 78 women without hot flashes were randomized to receive transdermal estradiol gel (1 g/day), oral estradiol alone (2 mg/day), oral estradiol combined with medroxyprogesterone acetate (MPA; 5 mg/day), or placebo for 6 months. Time- and frequency-domain measures of HRV were assessed using 24-hour electrocardiographic recordings at baseline and after hormone therapy. RESULTS: At baseline, the cardiac variables were similar in women with and without hot flashes. In women with hot flashes, the mean 24-hour heart rate and nighttime heart rate showed a tendency toward reduction in estradiol-only users compared with those taking placebo and those taking estradiol combined with MPA. In women with hot flashes, oral estradiol versus transdermal estradiol reduced nighttime HRV in the time domain (triangular index, -27 ± 36 vs +8 ± 36, P = 0.042). In women without hot flashes, the use of oral estradiol with MPA reduced time-domain HRV (SD of all normal-to-normal intervals; -11 ± 13 ms, P = 0.048, and square root of the mean of the sum of the squares of differences between adjacent normal-to-normal intervals; -6 ± 8 ms, P = 0.036). The women with hot flashes had more supraventricular ectopic beats when using oral estradiol with MPA than when using oral estradiol only (71 ± 128 vs 12 ± 11, P = 0.018). CONCLUSIONS: Oral estrogen, especially when combined with MPA, may have adverse effects on HRV in women with and without hot flashes, whereas transdermal estradiol showed no such effects. Furthermore, women with hot flashes receiving oral estrogen combined with MPA are possibly more prone to cardiac arrhythmias than are women using estrogen only.

Effect of positive end-expiratory pressure on regional ventilation distribution during bronchoconstriction in rabbit studied by synchrotron radiation imaging.

OBJECTIVE: To assess the effects of positive end-expiratory pressure on regional ventilation distribution in normal lung and after histamine-induced bronchoconstriction. DESIGN: Experimental study. SETTING: International research laboratory. SUBJECTS: Six healthy New Zealand rabbits weighing 2.5 ± 0.1 kg. INTERVENTIONS: Rabbits were anesthetized, tracheostomized, paralyzed, and mechanically ventilated. Synchrotron radiation computed tomography images of tissue density and specific ventilation were acquired using K-edge subtraction imaging with inhaled stable xenon gas in middle and caudal thoracic levels on 0 and 5 cm H(2)O positive end-expiratory pressure at baseline and twice after histamine inhalation. MEASUREMENTS AND MAIN RESULTS: At baseline, a positive end-expiratory pressure of 5 cm H(2)O significantly increased lung volume. Histamine inhalation caused patchy areas of decreased specific ventilation, including some areas with no ventilation. After histamine, positive end-expiratory pressure significantly increased the area of well-ventilated lung regions and decreased the heterogeneity of specific ventilation. This improvement went together with a significant but limited increase in the area of hyperinflated lung zones. CONCLUSIONS: The findings of this study suggest that in mechanically ventilated rabbit with severely heterogeneous bronchoconstriction, a positive end-expiratory pressure of 5 cm H(2)O significantly improves regional ventilation homogeneity through dilation of flow-limited airways and recruitment of closed airways.

Cardiovascular autonomic responsiveness in postmenopausal women with and without hot flushes.

OBJECTIVES: During menopausal transition autonomic balance is known to shift towards sympathetic dominance, but the role of vasomotor hot flushes in this phenomenon is not understood. We compared cardiovascular autonomic responsiveness between women with and without hot flushes. STUDY DESIGN AND MAIN OUTCOME MEASURES: One hundred fifty recently postmenopausal healthy women with varying degree of hot flushes (none, mild, moderate, severe) underwent comprehensive cardiovascular autonomic nervous testing (controlled and deep breathing, active orthostatic test, Valsalva manoeuvre and handgrip test) assessing both sympathetic and parasympathetic activity. The responses of heart rate, heart rate variability and blood pressure in these tests were evaluated. RESULTS: Responses in heart rate showed differences between the study groups only in the Valsalva manoeuvre where the tachycardia ratio in all symptomatic women was lower (p=0.041) than in women without hot flushes. Neither change in the heart rate variability analyses nor the blood pressure responses were affected by hot flush status. However, there was a non-significantly higher maximum systolic (140 (112-182)mmHg vs. 135 (102-208)mmHg) and diastolic blood pressure (94 (72-112)mmHg vs. 90 (66-122)mmHg) following the handgrip test in women without hot flushes vs. all the symptomatic women. CONCLUSIONS: Menopausal hot flushes seem to be associated with a possibly increased sympathetic preponderance without an effect on parasympathetic activity in cardiovascular autonomic responses. This may imply a potentially negative impact on cardiovascular health in women experiencing hot flushes.

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.

Acute cigarette smoke inhalation blunts lung responsiveness to methacholine and allergen in rabbit: differentiation of central and peripheral effects.

Despite the prevalence of active smoking in asthmatics, data on the short-term effect of acute mainstream tobacco smoke exposure on airway responsiveness are very scarce. The aim of this study was to assess the immediate effect of acute exposure to mainstream cigarette smoke on airway reactivity to subsequent nonspecific and allergenic challenges in healthy control (n = 5) and ovalbumin-sensitized rabbits (n = 6). We combined low-frequency forced oscillations and synchrotron radiation CT imaging to differentiate central airway and peripheral airway and lung parenchymal components of the response to airway provocation. Acute exposure to smoke generated by four successive cigarettes (CS) strongly inhibited the central airway response to subsequent IV methacholine (MCh) challenge. In the sensitized animals, although the response to ovalbumin was also inhibited in the central airways, mainstream CS did not blunt the peripheral airway response in this group. In additional groups of experiments, exposure to HEPA-filtered CS (n = 6) similarly inhibited the MCh response, whereas CO (10,000 ppm for 4 min, n = 6) or nitric oxide inhalation instead of CS (240 ppm, 4 x 7 min, n = 5) failed to blunt nonspecific airway responsiveness. Pretreatment with alpha-chymotrypsin to inhibit endogenous VIP before CS exposure had no effect (n = 4). Based on these observations, the gas phase of mainstream cigarette smoke may contain one or more short-term inhibitory components acting primarily on central airways and inhibiting the response to both specific and nonspecific airway provocation, but not on the lung periphery where both lung mechanical parameters, and synchrotron-imaging derived parameters, showed large changes in response to allergen challenge in sensitized animals.

Quality of life following lobectomy or bilobectomy for non-small cell lung cancer, a two-year prospective follow-up study.

Surgery for non-small cell lung cancer (NSCLC) is associated with a significant negative impact on health-related quality of life (HRQoL), but only a few published studies evaluate the long-term HRQoL and its association with preoperative pulmonary function tests (PFTs). We conducted a prospective study, with 53 patients undergoing lobectomy (n=49) or bilobectomy (n=4) for NSCLC, between May 2002 and September 2005. The 15D HRQoL instrument was administered preoperatively, and 3, 12, and 24 months postoperatively. Preoperative PFTs were recorded. We also compared the preoperative HRQoL results to an age-standardized general population. The two-year survival was 81%, 43/53 patients. Sustained impairment of HRQoL was noted two years after the surgery. No correlation emerged between preoperative PFTs and postoperative HRQoL. No differences were observed between stages I-II and stage III patients. Thus, lobectomy and bilobectomy are associated with significant sustained decrease especially in breathing, sleeping, usual activities, mental function, vitality and sexual activity, and in the overall HRQoL. These findings maybe used as preoperative patient information to emphasize the long-term consequences of lung cancer surgery.

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.

Association between vasomotor hot flashes and heart rate variability in recently postmenopausal women.

OBJECTIVE: The aim of this study was to investigate whether cardiovascular autonomic reactivity and risk profile are associated with the frequency and severity of hot flashes in recently postmenopausal women. METHODS: A total of 150 postmenopausal women with varying degrees of severity of hot flashes (none, mild, moderate, or severe) underwent 24-hour electrocardiographic recording. The function of the autonomic nervous system was assessed via heart rate variability in time and frequency domains. The effects of hot flashes on cardiac autonomic function were studied by assessing heart rate variability in the presence and absence of symptoms. RESULTS: There were no differences in mean heart rate, heart rate extremes, or total number of ectopic beats between women without and women with mild, moderate, or severe hot flashes. However, most women (14/17, 82%) with frequent ventricular ectopic beats and all women with ventricular runs belonged to the symptomatic groups. Although there were no differences in 24-hour or nighttime heart rate variability between the study groups, the very-low-frequency spectral component of heart rate variability increased by 72% (P < 0.001) during the hot flash period compared with the control period and was accompanied by an increase in heart rate (3%; P < 0.001). CONCLUSIONS: Cardiovascular risk markers based on heart rate variability failed to show an association with the frequency and severity of hot flashes in recently postmenopausal women. However, during a hot flash episode, there were signs of altered autonomic control of heart rate, which may be involved in the regulatory mechanisms of hot flashes.

Methacholine and ovalbumin challenges assessed by forced oscillations and synchrotron lung imaging.

RATIONALE: Methacholine (Mch) is routinely used to assess bronchial hyperreactivity; however, little is known about the differences in the lung response pattern between this provocation and that observed with ovalbumin (Ova) after allergic sensitization. OBJECTIVES: To compare (1) the central versus peripheral effects of Mch and Ova within the lung by combining measurements of airway and tissue mechanics with synchrotron radiation (SR) imaging, and (2) to assess the extent to which mechanical and imaging parameters are correlated. METHODS: We used the low-frequency forced oscillation technique and SR imaging in control (n = 12) and ovalbumin-sensitized (n = 13) rabbits, at baseline, during intravenous Mch infusion (2.5 microg/kg/min, 5.0 microg/kg/min, or 10.0 microg/kg/min), after recovery from Mch, and after intravenous Ova injection (2.0 mg). We compared intravenous Mch challenge with inhaled Mch (125 mg/ml, 90 s) in a separate group of control animals (n = 5). MEASUREMENTS AND MAIN RESULTS: Airway conductance and tissue elastance were measured by low-frequency forced oscillation technique. The central airway cross-sectional area, the ventilated alveolar area, and the heterogeneity of specific ventilation were quantified by SR imaging. Mch infusion induced constriction predominantly in the central airways, whereas Ova provocation affected mainly the peripheral airways, leading to severe ventilation heterogeneities in sensitized animals. Mch inhalation affected both conducting and peripheral airways. The correlations between airway conductance and central airway cross-sectional area (R = 0.71) and between tissue elastance and ventilated alveolar area (R = -0.72) were strong. CONCLUSIONS: The pattern of lung response caused by intravenous Mch and Ova are fundamentally different. Although inhaled Mch induces a heterogeneous lung response similar to that observed with intravenous allergen, these similar patterns are due to different mechanisms.

Paradoxical conducting airway responses and heterogeneous regional ventilation after histamine inhalation in rabbit studied by synchrotron radiation CT.

We studied both central conducting airway response and changes in the distribution of regional ventilation induced by inhaled histamine in healthy anesthetized and mechanically ventilated rabbit using a novel xenon-enhanced synchrotron radiation computed tomography (CT) imaging technique, K-edge subtraction imaging (KES). Images of specific ventilation were obtained using serial KES during xenon washin, in three axial lung slices, at baseline and twice after inhalation of histamine aerosol (50 or 125 mg/ml) in two groups of animals (n = 6 each). Histamine inhalation caused large clustered areas of poor ventilation, characterized by a drop in average specific ventilation (sV(m)), but an increase in sV(m) in the remaining lung zones indicating ventilation redistribution. Ventilation heterogeneity, estimated as coefficient of variation (CV) of sV(m) significantly increased following histamine inhalation. The area of ventilation defects and CV were significantly larger with the higher histamine dose. In conducting airways, histamine inhalation caused a heterogeneous airway response combining narrowing and dilatation in individual airways of different generations, with the probability for constriction increasing peripherally. This finding provides further in vivo evidence that airway reactivity in response to inhaled histamine is complex and that airway response may vary substantially with location within the bronchial tree.