Reduced airway distensibility, fixed airflow limitation, and airway wall remodeling in asthma.

The airways of individuals with asthma are less distensible than normal and it has been assumed that this may be due to airway remodeling associated with chronic inflammation, although there are currently no available data directly relating these two aspects of asthma. We have therefore carried out a study of the relationship between airway distensibility (DeltaVD) and subepithelial reticular basement membrane (RBM) thickening as an index of airway remodeling, in a group of patients with relatively mild but symptomatic asthma. Our methods included a cross-sectional study of DeltaVD in patients with mild to moderate atopic asthma, with matched airway biopsy for structural components. We confirmed that DeltaVD was lower in patients with asthma than in normal individuals (19.8 +/- 1.1 versus 24.1 +/- 1.5; p < 0.05) and that RBM thickness was increased in patients with asthma (9.1 +/- 2.2 versus 7.7 +/- 1.2 microm; p < 0.01). There was a negative correlation between DeltaVD and RBM thickness in asthma (r = -0.37, p = 0.03) and positive correlations between percent predicted postbronchodilator large and small airway function (for percent predicted FEV(1 )versus DeltaVD, r = 0.59, p < 0.001). We conclude that, cross-sectionally, DeltaVD was related to airway remodeling (RBM thickening) and airflow limitation (percent predicted large and small airway function). Our findings support the hypothesis that DeltaVD is a physiologic test that is reflective of airway remodeling.     

Clonidine induces upper airway closure in awake goats

We examined the effects of the alpha(2)-adrenoceptor (alpha(2)-AR) agonist clonidine on pressure-flow relationships in the upper airway. Inspired and expired airflows, subglottic tracheal pressure (PTR), mask pressure and middle pharyngeal constrictor (MPC) and diaphragm electromyogram (EMG) activities were recorded in awake standing goats. Clonidine-induced central apneas were always associated with continuous tonic activation of the MPC. Subglottic PTR during expiration increased progressively in a dose-dependent manner after clonidine administration. In all cases, positive subglottic PTR was maintained throughout the duration of clonidine-induced apneas and was sufficient to retard or prevent expiratory flow during early and mid-expiration indicating complete airway closure. The effects of clonidine were reversed by selective alpha(2)-AR blockade with SKF-86466. Central apneas after spontaneous augmented breaths (sighs) were associated with continuous tonic activation of the MPC throughout the duration of the prolonged TE intervals. However, subglottic PTR during expiration was not significantly different from control breaths and there was no evidence of increased expiratory airway resistance or delayed expiratory flow. We conclude that continuous tonic activation of pharyngeal adductor muscles appears to be a constant feature of central apnea in the awake goat independent of the initiating cause of the apnea. However, our data suggest that MPC activation alone may not be sufficient to cause complete closure of the upper airway during central apnea.     

Bronchial hyperresponsiveness, airway inflammation, and airflow limitation in endurance athletes

BACKGROUND: Whereas a high prevalence of bronchial abnormalities has been reported in endurance athletes, its underlying mechanisms and consequences during exercise are still unclear. STUDY OBJECTIVES: The purpose of this study was to assess the following: (1) bronchial responsiveness to methacholine and to exercise; (2) airway inflammation; and (3) airflow limitation during intense exercise in endurance athletes with respiratory symptoms. DESIGN: Cross-sectional observational study. SETTING: Lung function and exercise laboratory at a university hospital. PATIENTS AND MEASUREMENTS: Thirty-nine endurance athletes and 13 sedentary control subjects were explored for the following: (1) self-reported respiratory symptoms; (2) bronchial hyperresponsiveness (BHR) to methacholine and exercise; (3) airflow limitation during intense exercise; and (4) bronchial inflammation using induced sputum and nitric oxide (NO) exhalation. RESULTS: Fifteen athletes (38%) showed BHR to methacholine and/or exercise in association with bronchial eosinophilia (mean [+/- SD] eosinophil count, 4.1 +/- 8.5% vs 0.3 +/- 0.9% vs 0%, respectively), higher NO concentrations (19 +/- 10 vs 14 +/- 4 vs 13 +/- 4 parts per billion, respectively), a higher prevalence of atopy, and more exercise-induced symptoms compared with non-hyperresponsive athletes and control subjects (p < 0.05). Furthermore, airflow limitation during intense exercise was observed in eight athletes, among whom five had BHR. Athletes with airflow limitation reported more symptoms and had FEV1, FEV1/FVC ratio, and forced expiratory flow at midexpiratory phase values of 14%, 9%, and 29%, respectively, lower compared with those of nonlimited athletes (p < 0.05). CONCLUSION: BHR in endurance athletes was associated with the criteria of eosinophilic airway inflammation and atopy, whereas airflow limitation during exercise was primarily a consequence of decreased resting spirometric values. Both BHR and bronchial obstruction at rest with subsequent expiratory flow limitation during exercise may promote respiratory symptoms during exercise in athletes.     

Association between neutrophilic airway inflammation and airflow limitation in adults with asthma

BACKGROUND: There is debate about the mechanisms of persistent airflow limitation in patients with asthma. Chronic inflammation is assumed to be important, although there is limited and contradictory information about the relationship between airway inflammation and postbronchodilator FEV1. METHODS: We have assessed the cross-sectional relationship between prebronchodilator and postbronchodilator FEV1 and measures of airway inflammation after allowing for the effects of potential confounding factors. Multivariate analysis was performed on data collected from 1,197 consecutive patients with asthma seen at the respiratory outpatient clinic at Glenfield Hospital between 1997 and 2004. Relationships between induced sputum total neutrophil and differential eosinophil cell counts, and prebronchodilator and postbronchodilator lung function were examined. RESULTS: Sputum total neutrophil but not differential eosinophil count was associated with lower postbronchodilator FEV1. Both differential eosinophil and total neutrophil count were associated with lower prebronchodilator FEV1. These effects were independent after adjustment for age, smoking, ethnicity, asthma duration, and inhaled corticosteroid use. A 10-fold increase in neutrophil count was associated with a 92 mL reduction (95% confidence interval, 29 to 158; p = 0.007) in postbronchodilator FEV1. CONCLUSIONS: In this large heterogeneous population of adults with asthma, we have shown that prebronchodilator FEV1 is associated with neutrophilic and eosinophilic airway inflammation, whereas sputum total neutrophil counts alone are associated with postbronchodilator FEV1. This supports the hypothesis that neutrophilic airway inflammation has a role in the progression of persistent airflow limitation in asthma and raises the possibility that this progression and the development of COPD share a common mechanism.     

Improvement in exercise endurance in patients with chronic airflow limitation using continuous positive airway pressure

To cope with the increased ventilatory demands of exercise, patients with severe expiratory flow limitation adopt strategies that ultimately place greater demands on their inspiratory muscles. Increased inspiratory muscle work may contribute to dyspnea causation and exercise limitation in such patients even before their ventilatory ceiling is attained. In this setting, continuous positive airway pressure (CPAP) should, by favorably affecting inspiratory muscle function and respiratory sensation, improve exercise performance. Six patients with chronic airflow limitation (CAL) (FEV1 +/- SD = 35 +/- 12% predicted) undertook constant-load, submaximal, cycle exercise at 50% of their predetermined maximal oxygen consumption: CPAP of 4 to 5 cm H2O was delivered during one exercise session and bracketed by one or two unassisted control sessions. In four patients, CPAP-assisted (4 to 5 cm H2O) exercise was bracketed by two unassisted control exercise sessions; two remaining patients undertook CPAP-assisted exercise and one unassisted control session. CPAP resulted in a significant increase in exercise endurance time (TLIM) (by 48%: CPAP TLIM (mean +/- SE) = 8.82 +/- 1.90 min; averaged control TLIM = 5.98 +/- 1.23 min (p less than 0.01). CPAP effectively ameliorated exertional dyspnea in the majority of patients; selected dyspnea ratings (Borg scale) during control (final minute) and CPAP at isotime, at comparable levels of ventilation, were (mean +/- SD) 7.83 +/- 2.25 and 5.5 +/- 2.2, respectively (p less than 0.025). Breathing frequency fell significantly during CPAP application (at isotime) by 17% (p less than 0.02); other steady-state ventilatory variables and end-expiratory lung volumes were not significantly different during CPAP and control.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expiratory flow limitation in awake sleep-disordered breathing subjects.

Increased upper airways (UA) collapsibility has been implicated in the pathogeny of sleep-disordered breathing (SDB). An increased UA instability during expiration has recently been shown in healthy subjects. The present study assessed UA collapsibility in SDB patients by applying negative pressure during expiration. Full-night polysomnography was performed in 16 subjects (all snorers) with a wide range of SDB, and in six healthy control subjects. Physical examination, spirometry, and maximal inspiratory and expiratory flow rates were within normal limits for all 22 subjects. Negative expiratory pressure (NEP) (-5 cmH2O) was applied during quiet breathing in seated and supine position. Flow limitation (FL) during NEP was expressed as the percentage of tidal volume during which expiratory flow was less than or equal to the flow recorded during quiet breathing (%FL). The mean desaturation index (DI) of the 16 subjects was 27.3+/-26.4 (+/-sD) and the average FL in supine position was 38.4+/-37.9%. A close correlation between %FL supine during wakefulness and DI during sleep (r=0.84, p<0.001) was found. All obstructive sleep apnoea subjects had >30%FL supine. There was no FL in the six control subjects. In conclusion, negative expiratory pressure application during expiration appears to be a useful, noninvasive method for the evaluation of subjects with sleep-disordered breathing. Present results suggest that upper airway collapsibility can be detected in these subjects during wakefulness.     

Upper airway resistance during progressive hypercapnia and progressive hypoxia in normal awake subjects

Ventilatory motor output is known to influence the upper airway. Although inspiratory upper airway resistance decreases during progressive hypoxia or hypercapnia, the effects of hypoxia and hypercapnia on expiratory upper airway resistance remain unknown. In the present study, we attempted to examine whether the expiratory and the inspiratory upper airway resistances were modified in the same way by progressive hyperoxic hypercapnia or by progressive normocapnic hypoxia. Nine healthy subjects (five males, four females, 33+/-9 years) participated in the study. Inspiratory upper airway (iUAR) and expiratory upper airway resistances (eUAR) were calculated at flow 300 ml x s(-1). Both resistances were obtained during a baseline period and during progressive hyperoxic hypercapnia or progressive normocapnic hypoxia. In all subjects, iUAR and eUAR decreased significantly during hypercapnic or hypoxic challenge (P<0.05). eUAR was always lower than iUAR during hypercapnic challenge (P<0.0001) and during hypoxic challenge (P<0.0001). The authors conclude that expiratory upper airway resistance, as with inspiratory resistance, decreases during progressive hypercapnia or during progressive hypoxia. Pharyngeal dilator or constrictor muscle activities may be implicated.     

Factors associated with persistent airflow limitation in severe asthma.

Persistent airflow limitation can develop in nonsmoking patients with asthma. However, the prevalence and risk factors for airways obstruction with incomplete reversibility in asthma are unknown. We assessed the prevalence of persistent airflow limitation (defined as postbronchodilator FEV(1) or FEV(1)/VC < 75% predicted) in 132 nonsmoking outpatients with severe asthma visiting chest physicians in general hospitals in The Netherlands. They had used inhaled corticosteroids (> or = 1,600 microg/d) and/or daily oral prednisone and long-acting bronchodilators for > 1 yr. In addition, we examined whether persistent airways obstruction in these patients was associated with specific clinical characteristics (age at onset, smoking history, atopic status, bronchodilator reversibility, provocative concentration of histamine causing a 20% decrease in FEV(1) [PC(20)histamine]) or markers of inflammation (exhaled nitric oxide [NO], blood eosinophils, total IgE; and eosinophilia or neutrophilia in induced sputum). Multiple logistic regression analyses were used to calculate adjusted odds ratios (OR). Persistent airflow limitation was observed in 49% of the patients in the study, and apart from older age and longer asthma duration, was strongly associated with a sputum eosinophils percent > or = 2% (OR = 7.7; confidence interval [CI]: 2.4 to 25), PC(20)histamine < or = 1.0 mg/ml (OR = 3.9; CI: 1.2 to 13), and adult onset (> or = 18 yr) of asthma (OR = 3.3; CI: 1.2 to 9). Only sputum eosinophilia appeared to be independently associated with persistent airflow limitation (OR = 8.9; CI: 1.3 to 59). In conclusion, persistent airflow limitation is common in adult patients with severe asthma, and is associated with adult onset of the disease, airway hyperresponsiveness, and most importantly, sputum eosinophilia. These findings suggest that eosinophilic airway inflammation contributes to persistent airflow limitation in severe asthma. Whether reduction of sputum eosinophils with more vigorous treatment leads to a better prognosis in severe asthma is still an open question.     

Measuring health status in chronic airflow limitation

A health status instrument for use in clinical trials must be valid (measuring what it is supposed to measure) and responsive (able to detect clinically important change). Approaches to measuring health status in clinical trials include using a battery of instruments, a general instrument which provides a profile of the patient's health, an instrument that generates a health utility, or an instrument that focuses on the problems associated with a particular disease. Disease-specific instruments have been used in clinical trials in chronic airflow limitation (CAL). The Oxygen Cost Diagram is simple and easy to administer, but responsiveness and validity are unproven. The Transition Dyspnoea Index is valid and responsive, but is difficult to use in trials in which multiple measurements are desired. The Chronic Respiratory Disease Questionnaire has proved valid and responsive in controlled trials in CAL patients. Health status measures should be included in all clinical trials in CAL.     

Breathlessness in patients with severe chronic airflow limitation. Physiologic correlations.

We wished to identify the physiologic abnormalities that distinguish severely breathless (SB) patients with chronic airflow limitation (CAL) from mildly breathless (MB) patients. Thirty-seven patients with stable, advanced CAL (FEV1 = 38 +/- 10 percent predicted, mean +/- SD) were separated into two distinct groups, SB and MB, solely on the basis of their baseline dyspnea index (BDI). BDI ratings in SB (n = 17) and MB (n = 20) patients were 2.5 +/- 1.5 and 8.5 +/- 1.5 (mean +/- SD), respectively (p less than 0.001). Groups were compared with respect to pulmonary function, breathing pattern parameters, arterial blood gases (ABGs), and responses to progressive exercise. Steady-state gas-exchange parameters were measured in a subgroup of 16 patients during exercise. There were no significant intergroup differences in dynamic flows, plethysmographic lung volumes, ABGs, resting ventilation, or breathing pattern parameters. However, the SB group had significantly lower single-breath diffusing capacities for carbon monoxide (Dco) (by an average of 50 percent, p less than 0.001), together with significantly higher resting ventilatory equivalents for carbon dioxide (VE/VCO2) (by 17 percent, p less than 0.01) and dead space to tidal volume ratios (by 11 percent, p less than 0.05). Ventilatory responses for a given metabolic load were, on average, 33 percent higher (p less than 0.05) in the SB group reflecting greater ventilation-perfusion inhomogeneity and wasted ventilation. The SB subgroup (n = 7), in contrast to the MB subgroup (n = 9), demonstrated significantly (p less than 0.01) greater O2 desaturation during exercise; PaO2 decreased in SB and MB at peak exercise by -13 +/- 7 mm Hg and -4 +/- 2 mm Hg (mean +/- SD), respectively. Stepwise regression analysis selected DCO and VE/VCO2 as the only predictors of breathlessness in this group, accounting for 52 percent of the variance in BDI (F-ratio = 18.49, p less than 0.001). Although the origin of breathlessness is multifactorial, variation in its intensity among patients with comparable levels of airflow limitation can be accounted for, in part, by underlying pathophysiologic differences. Severely breathless patients were characterized by lower resting diffusing capacities and accelerated ventilatory responses to exercise.     

High-dose inhaled albuterol in severe chronic airflow limitation

Higher doses of inhaled albuterol have been shown to cause slightly more bronchodilatation than standard doses from a metered-dose inhaler in patients with severe chronic airflow limitation. Higher doses, however, carry an increased risk of side effects, and the optimum dose balancing benefit and adverse effects have yet to be established. We have therefore looked at objective and subjective evidence of beneficial and adverse effects after 4 doses of albuterol in 30 patients with chronic bronchitis, severe airflow limitation, and less than 200 ml increase in FEV1 after 200 micrograms inhaled albuterol. Subjects were given placebo, 400 micrograms, 1 mg, 2 mg, and 4 mg albuterol by dry powder inhaler in random order on separate days in a double-blind study, and FEV1, relaxed VC, PEFR, 12-min walk distance, finger tremor, oxygen saturation, heart rate, and arrhythmias were measured at intervals over 6 h. With increasing doses of albuterol, there was a significant dose-related increase in FEV1, VC, and PEFR, the maximal mean changes being 196 ml, 480 ml, and 50 L/min, respectively. The duration of effect was longer with the higher doses. There was a dose-related increase in heart rate, tremor amplitude, and supraventricular ectopic beats and a dose-related fall in oxygen saturation. There was no drug-related effect on the frequency of ventricular ectopic beats either at rest or during the walk tests. The largest increases in walk distance occurred after the 1 and 2 mg doses and the least after the 4 mg dose.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of oral terbutaline in chronic airflow limitation

A randomized, double-blind, crossover study was conducted to assess the efficacy of five weeks' treatment with terbutaline, 15 mg daily, compared with placebo in 17 evaluable patients with moderate to severe chronic airflow limitation (CAL) with a minor reversible component. A significant improvement after terbutaline treatment compared with placebo was observed in subjective assessments of breathlessness after two of the activities of daily living, and in daily peak flow measurements recorded in patient diaries. At the clinical assessment after five weeks' terbutaline therapy, 12 of 17 patients had improved pulmonary symptom scores compared with placebo, and a slight increase in FEV1 was observed relative to placebo (0.09 L, p less than 0.05). Thus, five weeks' treatment with oral terbutaline in patients with CAL resulted in significant improvements in several subjective assessments, despite a lack of effect on the majority of the objective variables.     

Assessing physiological benefit from domiciliary nebulized bronchodilators in severe airflow limitation.

In steroid resistant chronic obstructive pulmonary disease (COPD) we assessed the effect of q.i.d. domiciliary nebulized fenoterol (F) 1.25 mg and ipratropium (I) 0.5 mg for three weeks in a placebo-controlled, randomized, double-blind, crossover study. The twenty patients studied (mean forced expiratory volume in one second (FEV1) 0.8 l) all showed less than 20% increase in FEV1 to 200 micrograms inhaled salbutamol (S) and less than 20% increase in peak expiratory flow rate (PEFR) after 2 weeks prednisolone therapy. Respiratory function tests, 5 min walking distance (5 MWD), visual analogue scales (VAS) for breathlessness, oxygen cost diagrams and reversibilities were performed weekly for three weeks with patients on their usual therapy, after three weeks domiciliary F+I, after three weeks saline and, finally, after a further three weeks on usual therapy again. Primary end-points, selected prior to unblinding, were mean home twice daily PEFR, trapped gas volume, FEV1 and 5 MWD. Home PEFR rose from 164 l.min-1 on saline to 196 l.min-1 on F+I (p = 0.0001). Secondary end-point analysis revealed a fall in home inhaler usage and a rise in VAS. Using the criterion of +15% and greater than 20 l.min-1 increase in home PEFR, 11 out of 20 patients had a "positive" trial. We suggest that such patients, but not others, benefit from long-term, nebulized beta 2-agonist and ipratropium. Trials using home PEFR recordings should be used to identify them.     

Effect of intravenous hydrocortisone on nocturnal airflow limitation in childhood asthma.

Low endogenous cortisol levels appear to contribute to the pathophysiology of nocturnal asthma. Lower cortisol levels are associated with lower forced expiratory volume in one second (FEV1) levels in children with asthma. The aim of the present study was to identify whether substitution of low serum cortisol with intravenous hydrocortisone decreases 24-h FEV1 variation and/or indirect measures of airway inflammation. Hydrocortisone was given over 24 h in a double-blind randomised crossover design to 26 subjects. FEV1 was measured every 4 h during 24 h; blood eosinophils and airway responsiveness to methacholine and adenosine 5'-monophosphate (AMP) were measured at 04:00 h and 16:00 h. Cortisol levels increased during the night and morning hours. FEV1 values were higher at all time points in children with nocturnal asthma (n=10; 24-h FEV1 variation > or = 15%) which was significant at 08:00 h, unlike in the non-nocturnal asthma (NA-) group (n=16). Numbers of eosinophils (10(9) x L(-1)) at 04:00 h decreased in the asthma group (median 0.61 (range 0.05-1.42) versus 0.52 (0.05-1.79)). Provocative dose causing a 20% fall in FEV1 (PD20) methacholine did not change, whereas PD20 AMP improved only at 16:00 h in the NA- group (72.0 (0.13-144.0) versus 144.0 (2.25-144.0) mg x mL(-1)). These results show that substitution of lower endogenous 24-h values of cortisol contribute to higher forced expiratory volume in one second values and a decrease of blood eosinophils as an inflammatory marker in more severe airway obstruction.     

Exercise capacity and ventilatory, circulatory, and symptom limitation in patients with chronic airflow limitation.

Dyspnea, leg effort (Borg 0 to 10 scale), ventilation, and heart rate (VEmax/VEcap; HRmax/HRcap expressed as a percentage of capacity) were measured at maximal exercise (cycle ergometer) in 97 patients with chronic airflow limitation (CAL) (FEV, 46.6 +/- 14.23% of predicted) and compared with 320 matched control subjects. Patients with CAL achieved a maximum power output of 86 +/- 39.5 W (60 +/- 23.2% of predicted) compared with 140 +/- 37.5 W (98 +/- 14.5% of predicted) in controls (p less than 0.0001), VEmax/VEcap was 72 +/- 19.3% compared with 53 +/- 18.6% (p less than 0.0001), and HRmax/HRcap was 76 +/- 13.5% compared with 82 +/- 13% (p less than 0.001). These findings were expected. The median intensity of dyspnea was 6 (severe to very severe) and leg effort was 7 (very severe) in both groups, and these findings were unexpected. The patients with CAL were handicapped by an increase in both dyspnea and peripheral muscular effort relative to the actual power output. The rating of dyspnea exceeded leg effort in 25 (26%) of CAL versus 69 (22%) control subjects: the rating of leg effort exceeded dyspnea in 42 (43%) CAL and 117 (36%) control subjects; both were rated equally in 30 (31%) CAL and 134 (42%) control subjects, respectively (NS). VEmax/VEcap and HRmax/HRcap were not significantly different in those limited by dyspnea, leg fatigue, or a combination of both. All values are expressed +/- SD.     

Upper airway obstruction during sleep in normal subjects after selective topical oropharyngeal anesthesia

Previous animal studies support the presence of an upper airway reflex mechanism that when blocked by topical anesthesia of the upper airway results in upper airway occlusion. We sought a similar reflex mechanism in humans. Nine normal male volunteers 20 to 28 yr of age underwent 3 successive overnight sleep studies: a control study (C); a study in which selective topical oropharyngeal anesthesia (OPA) was achieved prior to sleep using a 10% lidocaine spray and 0.25% bupivocaine solution; a study in which selective nasal anesthesia (NA) was achieved prior to sleep using a mixture of 2% lidocaine and 0.25% bupivocaine solutions instilled into the nose while the nasal airway was positioned as the most dependent part of the upper airway. Total sleep times were similar during the 3 study nights as were the amounts of slow-wave and rapid-eye-movement (REM) sleep. Obstructive apneas and hypopneas (OAH) differed significantly between the 3 study nights [13(3.8), mean (SEM), during OPA as compared to 3(1.8) during C and 7(2.5) during NA; p less than 0.01 by ANOVA] and were most frequent during REM sleep. Total apneas and hypopneas also differed significantly between the 3 study nights [19(3.9) during OPA as compared to 8(2.1) during C and 14(3.9) during NA; p less than 0.01 by ANOVA]. Movement arousals terminating periods of abnormal respiration also differed significantly [21(6.1) during OPA as compared to 12(3.6) during C and 14(4.6) during NA; p less than 0.05 by ANOVA]. No subject, however, developed clinically significant sleep apnea or significant oxygen desaturation during sleep.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum periostin levels serve as a biomarker for both eosinophilic airway inflammation and fixed airflow limitation in well-controlled asthmatics

Objective: Periostin, a matricellular protein, is produced from airway epithelial cells and lung fibroblasts by IL-13. It has been suggested that periostin is involved in allergic inflammation and fibrosis. However, the usefulness of serum periostin measurement in the assessment of airway inflammation and remodeling and management of asthmatic patients is still debated. We aimed to determine whether serum periostin levels reflect eosinophilic airway inflammation and airway remodeling in asthma. Methods: We examined the relationship of serum periostin levels with clinical features, biomarkers for eosinophilic airway inflammation, fraction of exhaled nitric oxide (FeNO) levels and blood eosinophil counts, and pulmonary functions in 235 well-controlled asthmatic patients on inhaled corticosteroids (ICS) treatment. Results: Serum periostin levels were positively correlated with blood eosinophil counts (%) and age (r = 0.36 and 0.23, respectively), and were negatively correlated with body weight and FEV₁/FVC (%) (r = ?0.24 and ? 0.23, respectively) in well-controlled asthmatic patients on ICS treatment (daily dose of 453 µg equivalent to fluticasone propionate). Blood eosinophil counts and serum periostin levels were similarly associated with increased FeNO levels (≥40 ppb) in the asthmatics. Serum periostin levels were better associated with fixed airflow limitation (FEV₁/FVC ratio <70%) than FeNO levels, blood eosinophil counts or total IgE levels in the asthmatics. Multivariate analysis showed that fixed airflow limitation was significantly associated with high serum periostin levels (≥97 ng/ml) (Odds ratio 3.2). Conclusions: Serum periostin levels serve as a biomarker for both eosinophilic airway inflammation and fixed airflow limitation in well-controlled asthmatics on ICS treatment.