The effect of cigarette smoking on exhaled nitric oxide in mild steroid-naive asthmatics.

STUDY OBJECTIVES: It has been demonstrated previously that exhaled nitric oxide (eNO) is increased in steroid-naive asthmatics and that inhaled steroids reduce eNO in these patients. Cigarette smoking has also been reported to reduce the eNO in healthy volunteers. Recently a correlation has been demonstrated between eNO and airway hyperresponsiveness in steroid-naive, mild asthmatics. We hypothesized that cigarette smoking would reduce the eNO level in steroid-naive asthmatics and might, therefore, affect the correlation between eNO and airway hyperresponsiveness. DESIGN: Comparison of eNO in healthy smoking and nonsmoking volunteers with the level of eNO in steroid-naive and steroid-treated asthmatics. Correlate the eNO level with the provocative concentration of histamine causing a 20% fall in FEV1 (PC20hist) in the asthmatic smoking and nonsmoking patients. SETTING: University outpatient asthma clinic. PATIENTS AND METHODS: eNO levels and PC20hist were measured in three different asthmatic patient groups (group A = 29 steroid-naive, nonsmoking asthmatics; group B = 19 steroid-treated, nonsmoking asthmatics; and group C = 13 smoking, steroid-naive asthmatics) and in two healthy volunteer groups (group D = 18 nonsmoking; and group E = 16 smoking). RESULTS: eNO in group A was significantly increased compared with the values in groups B and D (21.8+/-12.7, 12.8+/-4.9, and 10.6+/-2.2 parts per billion [ppb], respectively). Cigarette smoking decreased eNO in healthy volunteers (7.4+/-1.8 ppb, group E) as well as in steroid-naive asthmatics (12.7+/-5.1 ppb, group C). There was a significant correlation between eNO and PC20hist in group A (r = -0.45, p < 0.05); this correlation was, however, lost in both groups B and C. CONCLUSION: Cigarette smoking and inhaled steroids reduce the eNO in patients with mild asthma to a comparable extent. Because the correlation between eNO and airway hyperresponsiveness was lost in steroid-treated and smoking, steroid-naive asthmatics, we question the value of eNO as a marker of airway inflammation, at least in mild asthmatics who are already being treated with inhaled steroids or who are currently smoking.     

Exhaled nitric oxide is age-dependent in asthma

We determined whether the exhaled nitric oxide (eNO) level in asthmatics is age-dependent. Eighty-seven asthmatic patients aged 2-41 years were studied. Hyperreactivity to adenosine 5'-monophosphate (AMP) was used to confirm asthma (相似文献   

Comparison of add-on therapy to inhaled fluticasone propionate in children with asthma: residual volume and exhaled nitric oxide as outcome measures.

The purpose of this study was to evaluate changes in lung function and fractional exhaled nitric oxide (FeNO) in children with mild to moderate persistent asthma treated with low-dose inhaled steroids but still manifesting significantly increased residual volume (RV). This was a crossover study evaluating lung function and FeNO before and after a 2-week crossover therapy period by adding either montelukast or salmeterol to inhaled fluticasone propionate in 12 children with asthma. Salmeterol increased forced expiratory volume at 1 second (FEV(1)) and decreased RV without effects on eNO. Addition of montelukast produced a statistically significant decrease both for RV (from 191.7 +/- 60.8% to 132.4 +/- 36.1%; p = 0.03) and for eNO (from 14.0 +/- 6.3 ppb to 8. 5+/- 5.0 ppb; p < 0.01). No effect was observed for the montelukast treatment period in FEV(1) and forced expiratory flow at 25-75%. Add-on therapy may reduce RV and decrease levels of FeNO, leading to consideration of a possible anti-inflammatory additive effect that could improve the control of the disease.     

Exhaled nitric oxide as a noninvasive assessment of chronic cough.

Exhaled nitric oxide (ENO) has been suggested as a marker of airway inflammation. This study aimed to evaluate the role of ENO in the investigation of chronic cough. We measured ENO in 38 adult patients reporting chronic cough, in 23 healthy control subjects, and in 44 asthmatics. In addition to the regular investigation, ENO was measured by a chemiluminescent analyzer using the restricted breath technique. In the chronic cough group, 30 were considered as nonasthmatic, whereas asthma was diagnosed in eight by a positive methacholine challenge. ENO values were significantly higher in patients with chronic cough attributable to asthma as compared with those with chronic cough not attributable to asthma and to healthy volunteers (75.0 ppb; 16.7 ppb; and 28.3 ppb, respectively). The sensitivity and specificity of ENO for detecting asthma, using 30 ppb as the ENO cutoff point, were 75 and 87%, respectively. The positive and negative predictive values were 60 and 93%, and the positive and negative likelihood ratios were 5.8 and 0.3, respectively. We conclude that ENO may have a role in the evaluation of chronic cough. In this group of patients, low ENO suggested little likelihood of asthma. The patients with chronic cough not attributable to asthma showed a low ENO value as compared with healthy volunteers and asthmatics.     

Relationship between exhaled nitric oxide levels and compliance with inhaled corticosteroids in asthmatic children

Levels of exhaled nitric oxide (eNO) are elevated in subjects with asthma and fall in response to oral or inhaled steroids. This study explored the possibility the measurement of eNO levels could be used to identify subjects who were not adhering to their treatment regimen. Twenty children with asthma attending the respiratory clinic were recruited. Each attended on four occasions 1 month apart when eNO levels were measured. A data logger attached to a pressurised metered dose inhaler was used to objectively monitor use of inhaled corticosteroids (ICSs). The correlation between day and dose compliance with eNO was assessed. The data demonstrated a weak but non-significant correlation between eNO and both day (r = 0.055, P = 0.67) and dose (r = 0.153, P = 0.23). A recorded value of eNO less than 12 was associated with day compliance rates of 3-97%. Of the 19 recorded eNO values greater than 12 ppb almost 80% were from subjects with a day compliance of less than 50% during the preceding month. Of the four values greater than 12 ppb and day compliance > 60% one subject had a poor inhaler technique, one had a mild viral exacerbation and one appeared to be associated with increase pollen exposure. The measurement of eNO may prove to be a useful tool in helping to manage children with asthma but further work is required to define its precise role. Elevated eNO levels in asthmatic children taking ICSs are likely to reflect poor compliance but confounding factors such as disease activity and inhaler technique need to be carefully considered.     

Usefulness of exhaled nitric oxide and sputum eosinophils in the long-term control of eosinophilic asthma

BACKGROUND: The aim of the present study was to treat unstable asthma according to exhaled nitric oxide (eNO) and induced-sputum eosinophils (sEos) levels to assess if this strategy is better than the conventional approach based on symptoms and function to achieve asthma control. METHODS: Fourteen patients with mild-to-moderate persistent asthma (6 men, 8 women) were recruited. During the recruitment visit, the patients, previously treated for asthma following Global Initiative for Asthma recommendations, underwent clinical evaluation and pulmonary function tests (PFTs). Then, after 4 weeks of washout from inhaled antiinflammatory treatment, the patients underwent a basal visit performing PFTs, challenge test to methacholine, and determination of eNO and sEos counts. These procedures were repeated after 3, 6, and 12 months while the patients were treated with inhaled steroids in a stepwise fashion according to eNO and sEos values. RESULTS: At the end of the study, a significant decrease in eNO and sEos was observed (57.2 +/- 32.8 parts per billion [ppb] vs 22.1 +/- 10.8 ppb, p < 0.01; and 27.1 +/- 27.1% vs 3.7 +/- 3.5%, p < 0.01, respectively). A close correlation (r2 = 0.41, p < 0.01) between the percentage change of eNO and sEos was observed only after 6 months. Patients treated according to the levels of these inflammatory markers had fewer symptoms and fewer exacerbations compared to those the year before when they were conventionally treated. CONCLUSIONS: Our results show the usefulness of eNO and sEos for titrating treatment in asthmatic patients in order to achieve better long-term control of the disease. The eNO decrease reflects adequately the reduction of sEos only after 6 months.     

Correlation between cough frequency and airway inflammation in children with primary ciliary dyskinesia

Cough is common in airway disease. We measured cough frequency in children with primary ciliary dyskinesia (PCD), to determine how accurately families assess this symptom; and to assess the relationship between cough frequency and airway inflammation, measured using induced sputum and exhaled nitric oxide (eNO). Twenty stable PCD children (7 boys), median age 10.8 years (interquartile range (IQR), 9-14), and 10 healthy control children, median age 12 years (IQR, 10.5-12.7), were recruited. ENO was measured using a chemiluminescence analyzer, with sputum induction with 3.5% saline. PCD children underwent ambulatory cough monitoring. Sputum neutrophils were higher in PCD (median, 70.3%; IQR, 55.3-78%) compared to controls (median, 27%; IQR, 24.5-33%; P = 0.004); cough frequency was higher (median episodes, 19; IQR, 11-22.5) compared to healthy children (median episodes, 6.7; IQR, 4.1-10.5; P < 0.001). Forced expiratory volume in 1 sec (FEV(1) percent predicted) and eNO were lower in PCD (median, 63%; IQR, 57-85%; P < 0.0001); eNO (median, 7.1 ppb (IQR, 4.8-19.1 ppb) vs. 12.4 ppb (IQR, 10.3-17.3 ppb), P = 0.043). Parental scoring of day and night cough correlated with recorded cough (r = 0.930, P < 0.0001, daytime; r = 0.711 for nighttime, P = 0.002). Visual analogue score and cough episodes also correlated positively (r = 0.906; P < 0.0001). There was a positive correlation between cough frequency and sputum neutrophil count in PCD (Spearman's r = 0.693, P < 0.002), but not percent FEV(1) or eNO. Stable PCD children have increased cough frequency and neutrophilic airway inflammation. In conclusion, cough frequency correlated with sputum neutrophils but not with FEV1 or eNO.     

Influence of inhaled steroids on pulmonary epithelial permeability to Tc99m-dTPA in atopic asthmatic children.

The lung permeability of asthmatic children has been reported to be similar, lower, or higher than that of healthy subjects. The aim of this study was to clarify these discrepancies and also assess the effect of inhaled steroids on lung permeability. Tc99m-diethylenetriaminepentaaceticacid (Tc99m-DTPA) clearance in children with mild unstable asthma (n = 13; mean age 9.3 +/- 0.7 years) was compared with that of a group of healthy subjects (n = 11; mean age 8.9 +/- 0.8 years). Symptom scores, forced-expiratory volume in the first second (FEV1), and peak expiratory flow rate variability (PEFR-v) of asthmatics were recorded and an inhaled steroid (budesonid) was recommended after first scintigraphic evaluation for 8 weeks. Two consecutive scintigraphic studies were performed before and after treatment. Symptoms, FEV1, and PEFR-v significantly improved throughout the study. Baseline DTPA clearance rate in the asthmatics was significantly higher from that of control group (1.3 +/- 0.2 and 0.7 +/- 0.1%/min, respectively) (p < 0.05). DTPA clearance rate of asthmatics significantly increased to 1.7 +/- 0.3%/min at end of inhaled therapy (p < 0.05). Our data show that DTPA clearance in unstable asthmatic children is significantly higher than that found in healthy subjects, and that a higher rate was obtained following inhaled steroid therapy. Thus, the clinical significance of these observations needs further studies to test whether DTPA clearance index is a valid tool for monitoring asthmatic children and to explore the mechanisms involved in radioaerosol clearance rates in pediatric asthma.     

Smoking and airway inflammation in patients with mild asthma.

STUDY OBJECTIVES: Cigarette smoking is common in asthmatic patients, and we investigated the impact of cigarette smoking on airway inflammation in asthma. DESIGN: Single-center observational study of airway inflammation in asthmatic and healthy smokers and nonsmokers. SETTING: Asthma research unit in a university hospital. PATIENTS OR PARTICIPANTS: Sixty-seven asthmatic and 30 nonasthmatic subjects classified as smokers or nonsmokers. Asthmatics had chronic, stable asthma and were not receiving inhaled or oral steroids at the time of the study. INTERVENTIONS: We examined induced-sputum cell counts and levels of interleukin (IL)-8 and eosinophilic cationic protein (ECP). Bronchial hyperreactivity was assessed using methacholine challenge. MEASUREMENTS AND RESULTS: Asthmatic smokers had higher total sputum cell counts than nonsmoking asthmatics and both smoking and nonsmoking healthy subjects. Smoking was associated with sputum neutrophilia in both asthmatics and nonasthmatics (median, 47% and 41%, respectively) compared with nonsmokers (median, 23% and 22%, respectively), and sputum IL-8 was increased in smokers compared with nonsmokers, both in subjects with asthma (median, 945 pg/mL vs 660 pg/mL, respectively) and in healthy subjects (median, 1,310 pg/mL vs 561 pg/mL, respectively). Sputum eosinophils and ECP levels were higher in both nonsmoking and smoking asthmatics than in healthy nonsmokers. In smoking asthmatics, lung function (FEV(1) percent predicted) was negatively related to both sputum IL-8 (r = - 0.52) and sputum neutrophil proportion (r = - 0.38), and sputum IL-8 correlated positively with smoking pack-years (r = 0.57) and percent neutrophil count (r = 0.51). CONCLUSIONS: In addition to the eosinophilic airway inflammation observed in patients with asthma, smoking induces neutrophilic airway inflammation; a relationship is apparent between smoking history, airway inflammation, and lung function in smoking asthmatics.     

Time-dependent changes in orally exhaled nitric oxide and pulmonary functions induced by inhaled corticosteroids in childhood asthma.

Exhaled nitric oxide levels are elevated in asthmatic children and decrease after inhaled steroid treatment. We evaluated the time-dependent changes in fractional exhaled nitric oxide concentration (FENO) and pulmonary function parameters following inhaled steroid therapy. Thirty-nine steroid-naive atopic patients (age 11.92+/-0.48 years) with mild intermittent asthma and 22 age-matched healthy controls were enrolled in the study; pulmonary functions and FE(NO) levels were measured. Low doses of inhaled steroids were prescribed to all asthmatic patients who were reevaluated in a second visit (between 10 and 40 days after the beginning of the treatment). At the enrolment, asthmatic patients had similar forced expiratory volume in 1 sec (FEV1) and forced vital capacity (FVC) values (p > 0.05) but reduced forced expiratory flows at 25-75% of the vital capacity (FEF(25-75%)) values, as compared to controls (p < 0.05). In addition, FE(NO) levels were significantly higher in asthmatics with respect to control subjects (30.8+/-3.0 and 4.0+/-0.5 ppb, respectively; p < 0.01). All asthmatics had FE(NO) levels higher than 8.8 ppb (i.e., > 2 standard deviations of the mean in controls). After steroid treatment, patients showed significant improvement of FEV1, FVC, and FEF(25-75%) (p = 0.0001; each comparison) and a reduction of FE(NO) levels (p = 0.0001). A weak significant correlation was found between percent decrease in FE(NO) levels and percent increase in FEV1 (r = 0.33, p = 0.04) or in FEF(25-75%) (r = 0.4, p = 0.01) after treatment. When changes in FE(NO) levels and in pulmonary function parameters were corrected for days of treatment, significant correlations were still present between percent decrease in FE(NO) levels and percent increase in FEV1 (r = 0.57, p = 0.0004) or percent increase in FEF(25-75%) (r = 0.45, p = 0.006). Sixteen of the 39 asthmatic patients were evaluated on two occasions after the beginning of treatment, at days 10 and 40. The significant reduction in FE(NO) levels (p < 0.01) and the significant increase in FEV1 and FEF(25-75%) values observed (p < 0.05) after 10 days did not further improve at day 40. These data show that it is possible to demonstrate early effects of low-dose inhaled steroids in asthmatic children using objective measurements of airway caliber and inflammation.     

Elevated nitrite in breath condensates of children with respiratory disease.

The aim of the study was to determine the differences in nitrite, in the exhaled breath condensates of healthy children and those children with asthma, cystic fibrosis (CF) and nonasthmatic, episodic cough. Breath condensates were obtained from 66 children (43 males:23 females, 3.1-16 yrs) and included 29 asthmatics, 12 clinically stable CF patients, 12 children with cough but not asthma and 13 healthy volunteers. The collected condensate was assayed colourimetrically using the Griess reaction to determine nitrite concentrations. Patients with CF (median: 5-95% percentiles; 2.02: 0.43-6.37 microM) or asthma (2.10: 0.63-5.45 microM) had significantly higher levels of nitrite compared to healthy subjects (0.41: 0.13-1.83 microM; p<0.05) or subjects with cough (0.75: 0.03-1.75 microM; p<0.05). Airway inflammation, as assessed by the nitrite in breath condensates, is present in children with asthma and cystic fibrosis, but not those children with nonasthmatic, episodic cough. Nitrite can be conveniently, cheaply and rapidly measured in breath condensates of children as young as 3 yrs of age, and may prove useful for the assessment of airway inflammation in children with respiratory disease.     

Exhaled nitric oxide in chronic obstructive pulmonary disease: relationship to pulmonary function.

The following study was undertaken in order to determine how exhaled nitric oxide (eNO) levels in former smokers with chronic obstructive pulmonary disease (COPD) compared to eNO levels in patients with asthma and in healthy nonsmoking volunteers. The study also aimed to determine any relationship between eNO levels in COPD and: 1) conventional measures of lung function; and 2) inhaled corticosteroid (ICS) use. In former smokers with COPD, nonsmokers with asthma and volunteers, eNO levels, spirometry, lung volumes, carbon monoxide diffusion capacity of the lung (DL,CO) and resting oxygen saturation (Sa,O2) were measured. Median eNO was significantly higher among patients with COPD than among healthy volunteers (p = 0.003) but lower than among patients with asthma (p < 0.01). There was no significant difference in eNO levels between COPD patients using ICS and those not using ICS. By contrast, eNO was lower among asthma patients who used ICS (median 32 parts per billion (ppb); 25-75% range 16-54) than among asthma patients who did not (51 ppb; 32-87) (p = 0.034). Among patients with COPD, eNO was inversely correlated with forced expiratory volume in one second, DL,CO and Sa,O2, and was positively correlated with the residual lung volume/total lung capacity ratio. Among patients with asthma, no significant correlations were found. Exhaled nitric oxide is increased in patients with chronic obstructive pulmonary disease, an increase that is influenced by structural abnormalities of tobacco-induced lung damage.     

Maternal atopic disease modifies effects of prenatal risk factors on exhaled nitric oxide in infants

In a prospective healthy birth cohort, we determined whether levels of exhaled nitric oxide (eNO) in healthy unselected infants at the age of 1 month were associated with maternal atopic disease and prenatal and early postnatal environmental exposures. Tidal eNO was measured in 98 healthy, unsedated infants (35 from mothers with atopy) (mean age +/- SD, 36.0 +/- 6.2 days) and was compared with histories taken in standardized interviews. eNO was higher in males compared with females (17.7 vs. 14.6 ppb, p = 0.042) and infants exposed to postnatal maternal smoking (+4.4 ppb, p = 0.027), adjusting for weight and tidal breathing parameters. Prenatal tobacco exposure was associated with higher eNO (+12.0 ppb, p = 0.01) in infants of mothers with asthma and lower eNO (-5.7 ppb) in infants of mothers without asthma (p for interaction < 0.0001). Coffee consumption in pregnancy decreased eNO (-6.0 ppb, p = 0.008) only in children of mothers with atopy (p for interaction = 0.015). Paternal atopy had no influence. In the early phase of immunologic development, before the onset of infections and allergic disease, the effect of prenatal or early postnatal environmental factors on eNO was modified by the presence of maternal atopic disease. This underlines the complex interaction of maternal and environmental factors in the development of airway disease.     

Comparison of exhaled nitric oxide,serum eosinophilic cationic protein,and soluble interleukin-2 receptor in exacerbations of pediatric asthma

The hypotheses tested in this study were that during acute asthma exacerbations (1) exhaled nitric oxide concentrations [eNO] are a more sensitive, noninvasive indicator of asthma disease activity than serum markers of inflammation such as eosinophil cationic protein (ECP) or soluble interleukin 2 receptor (sIL2R), and (2) elevated [eNO] are reduced after treatment with glucocorticoids (GC). Peak eNO levels were measured by chemiluminescence during slow expiration. Seven asthmatic subjects (mean age 11 yrs; mean morning FEV1 65% predicted) receiving inhaled GC, and with no radiographic evidence of acute sinusitis, were studied before and after a course of oral GC. Measurements of [eNO], ECP and sIL2R levels, and FEV1% were obtained before and after a course of GC. Six atopic nonasthmatic subjects (mean age 12 years; mean FEV1 94% predicted) and seven normal subjects (mean age 13 years; mean FEV1 100% predicted) were studied. The mean peak [eNO] level (parts per billion: ppb) for the asthma subjects before treatment (52 ± 5 ppb SEM) was greater than the value for both nonasthmatic atopic and normal subjects (16 ± 2 ppb and 14 ± 2 ppb SEM, respectively; P < 0.0001). There was no significant difference in ECP or sIL2R values between asthmatic subjects and either atopic or normal subjects (P > 0.05). Baseline pre-GC treatment ECP levels in the asthmatic subjects were significantly higher (P < 0.002) than post-GC treatment values. The mean peak [eNO] level in the asthmatic subjects declined after oral GC treatment to 14 ± 1 ppb (P < 0.0002) and was less than 2 ppb different from either control group (P > 0.75). We conclude that [eNO] is a more sensitive marker of asthma disease activity than ECP and sIL2R levels. In addition, [eNO] appears to be a more useful indicator of the beneficial response to GC therapy than these other measurements in pediatric asthma. Pediatr. Pulmonol. 1997; 24:305–311. © 1997 Wiley-Liss, Inc.     

Increased leukotrienes in exhaled breath condensate in childhood asthma

Cysteinyl leukotrienes (cys-LTs; LTC4, LTD4, and LTE4) are generated predominantly by mast cells and eosinophils and induce airway smooth muscle contraction, microvascular leakage, and mucous hypersecretion whereas leukotriene B4 (LTB4) is a potent chemoattractant of neutrophils. We measured cys-LTs and LTB4 in exhaled breath condensate from children aged 7-14 years including healthy nonatopic children (n = 11) and children with mild intermittent asthma (steroid naive, n = 11), mild persistent asthma (low-dose inhaled steroid treatment, n = 13), or moderate to severe persistent asthma (high-dose inhaled steroid treatment, n = 13). Exhaled LTB4 levels were increased in patients with mild and moderate to severe persistent asthma compared with patients with mild intermittent asthma (126.0 +/- 8.8 and 131.9 +/- 7.1 versus 52.7 +/- 3.8 pg/ml, p < 0.001 and p < 0.0001) and normal subjects (126.0 +/- 8.8 and 131.9 +/- 7.1 versus 47.9 +/- 4.1 pg/ml, p < 0.0001). Elevated exhaled cys-LT levels were found in patients with mild and moderate to severe persistent asthma compared with normal subjects (27.9 +/- 2.8 and 31.5 +/- 4.5 versus 18.5 +/- 0.5 pg/ml, p < 0.01 and p < 0.05). There was an inverse correlation between exhaled cys-LTs and LTB4 in patients with mild persistent asthma. We conclude that exhaled cys-LTs and LTB4 may be noninvasive markers of airway inflammation in pediatric asthma.     

The role of measurement of exhaled nitric oxide in asthma patients

The aim of the study was to evaluate exhaled nitric oxide levels (F(ENO)) in asthmatics and to establish the possible correlation of these measurements with clinical symptoms, disease severity, anti-inflammatory treatment and spirometric indices. The measurement of exhaled NO was performed using NO analyser model 280i, Sievers Instruments, Inc., USA. This measurement was based on the gas phase chemiluminescence reaction between NO and ozone. The investigations were performed on the group of 85 asthmatic patients (34 with chronic mild asthma, 31 with chronic moderate asthma, 20 with chronic severe asthma). F(ENO) level in healthy, non-smoking volunteers (46 persons--control group) was mean 12.9 +/- 4.6 ppB and it was statistically significant lower than in all groups of asthmatics. The highest F(ENO) levels were observed in patients with severe asthma (74 +/- 72 ppB). Statistically significant lower levels of ENO were obtained in patients with moderate (42 +/- 31 ppB) and mild asthma (49 +/- 43 ppB). In all groups of asthmatic patients higher levels of F(ENO) were observed in subjects with allergic asthma. In patients with mild and moderate asthma ENO levels were negatively correlated with the used dosage of inhaled steroids. Similar dependences were not noticed in patients with severe asthma. The measurement of exhaled nitric oxide levels provides a rapid, reproducible, non-invasive and reliable test, which is very useful in diagnosis and treatment monitoring in asthmatic patients.     

Inflammatory Subtypes in Asthma are Related to Airway Hyperresponsiveness to Mannitol and Exhaled NO

Asthma may be defined as eosinophilic or non-eosinophilic based on the presence of eosinophils in sputum. Recently a further classification into four inflammatory subtypes has been suggested. The aim of the present study was to describe the association between these inflammatory subtypes and markers of airway inflammation and hyperresponsiveness. In 62 adult non-smoking asthmatics, (18–65 yr) not taking inhaled steroids, sputum induction, bronchial challenge with mannitol and measurement of exhaled NO (eNO) were performed. Based on the eosinophil and neutrophil proportions in sputum, subjects were categorised into four inflammatory subtypes: Eosinophilic asthma: i.e., sputum eosinophils > 1.0%. Neutrophilic asthma: i.e., sputum neutrophils > 61%. Mixed granulocytic asthma: both increased eosinophils and neutrophils. Paucigranulocytic asthma: i.e., normal levels of both eosinophils and neutrophils. Among subjects with non-eosinophilic asthma, neutrophilic asthma was associated with low levels of eNO (Median (IQR): 12 ppb (8–27 ppb), whereas subjects with non-eosinophilic asthma of the paucigranulocytic subtype had levels of eNO (48 ppb (29–65 ppb)) that were comparable to subjects with eosinophilic asthma of the mixed granulocytic type (47 ppb (33–112 ppb). Purely eosinophilic asthma was associated with higher levels of eNO (77 ppb (37–122 ppb)). Furthermore, a low degree of airway hyperresponsiveness to mannitol was observed in neutrophilic asthma (PD₁₅: (Median (IQR) 512 mg (291–610 mg))), whereas it was moderate in paucigranulocytic asthma (238 mg (77–467 mg)) and comparable to eosinophilic asthma of the mixed granulocytic subtype (186 mg (35–355 mg)). The highest degree of AHR to mannitol was observed in purely eosinophilic asthma (107 mg (68–245 mg)). In conclusion, further subclassification of eosinophilic and non-eosinophilic asthma showed significant differences in airway hyperresponsiveness to mannitol and exhaled NO levels among the four inflammatory subtypes.     

Correlation between reversibility of airway obstruction and exhaled nitric oxide levels in children with stable bronchial asthma

Recent trials measuring exhaled nitric oxide (eNO) concentrations have suggested that it may be a useful measure of ongoing airway inflammation in patients with asthma. The purpose of this study was to examine the relationship between eNO levels and baseline as well as postbronchodilator spirometry, a measurement commonly used in the clinical setting to determine the severity of asthma and as a guide to therapeutic decisions. Forty-nine patients between the ages of 5-16 years with physician-diagnosed asthma who attended the pediatric pulmonary clinic for a routine asthma visit with spirometric evaluation were recruited for the study. eNO levels prior to spirometry were obtained before and after receiving inhaled beta(2) agonist. eNO samples were collected in impermeable bags (Tedlar) and assayed within 24 hr by chemiluminescence. Regression analysis was used to assess the relationships between pre- and postbronchodilator eNO and spirometric variables. eNO was also compared in patients receiving and not receiving inhaled corticosteroids (ICS), as well as those whose therapy had been increased after evaluation by a pediatric pulmonologist or allergist. We found no significant difference between the levels of eNO before and after inhalation of beta(2) agonist (P = 0.60 paired t-test). Positive correlation was found between eNO vs. percentage change in FEV(1) (r = 0.35, P = 0.01) and percentage change in FEF(25-75% )(r = 0.29, P = 0.04). A negative correlation was found between prebronchodilator FEV(1) and eNO (r = -0.29, P = 0.03). Patients on ICS had lower mean eNO levels (29.9 vs. 47.6 parts per billion (ppb), P = 0.053) than those not receiving ICS. Patients whose ICS therapy was increased had higher mean eNO levels (47.2 vs. 26.9 ppb, P = 0.018) than those not having ICS therapy increased. We suggest that eNO levels could be a clinically useful measurement of asthma severity and could be used as an adjunct to spirometry to determine appropriate treatment plans. Longitudinal clinical trials are needed to determine if eNO can enhance therapeutic decisions for asthmatic children.     

Real-life environmental tobacco exposure does not affect exhaled nitric oxide levels in asthmatic children.

Serial measurement of exhaled nitric oxide (eNO) has been shown to be a good noninvasive marker of asthma control. Active smoking decreases eNO levels. The effect of real-life environmental exposure to tobacco smoke (ETS) on eNO levels is not known. Our objective was to study the impact of environmental tobacco exposure on eNO levels in asthmatic and non-asthmatic children. Single breath off-line collection of eNO was performed in asthmatic and non-asthmatic children with and without ETS. Urine was collected for cotinine/nicotine analysis. Fifty-seven children were enrolled, of which 25 were asthmatic and 32 had smoke exposure. One active smoker was excluded from the data analysis. The mean eNO was 11.1 ppb (n = 31; SD = 18.5) in those passively exposed vs. 11.1 ppb (n = 25; SD = 19.9) among the unexposed (not statistically significant). The mean eNO was 6.1 (n = 32; SD = 4.4) among the non-asthmatics and 17.8 (n = 24; SD = 27.4) among the asthmatics (p = 0.02; CI: 1.9-21.6). Real-life environmental tobacco exposure does not appear to decrease eNO levels in asthmatic children. Off-line collection of exhaled nitric oxide with a Mylar collection device helps differentiate asthmatics from non-asthmatics.     

Nonspecific bronchial reactivity in asthmatic children depends on severity but not on age

Bronchial reactivity to inhaled methacholine was measured by the steady-state tidal breathing method in asthmatic children aged 1 to 17 yr. The children were divided into three clinical groups according to their minimal therapeutic requirements: mild asthma, children requiring infrequent treatment with inhaled beta-agonists (81 patients); moderate asthma, children requiring daily preventive treatment with either cromolyn sodium or slow-release theophylline (67 patients); and severe asthma, children requiring daily preventive treatment with oral or inhaled steroids (34 patients). They were also divided into three age groups: from 1 to 6 yr, tested by using bronchial provocation with tracheal auscultation (BPTA) to determine the methacholine concentration causing wheezing (PCW); and from 7 to 11 yr and 12 to 17 yr, using lung function testing to determine the concentration causing a 20% fall in FEV1 (PC20). For the whole group the mean level of bronchial reactivity to methacholine correlated inversely with the severity of bronchial asthma according to the minimal drug requirements (p less than 0.0001) and was similar over the whole age range (p less than 0.9965) for each severity grouping. In the older children the difference between moderate and severe asthma was not significant, but this may have been a result of the effect of corticosteroids in the severe group. We concluded that age has no significant effect on the methacholine response in asthmatic children over a wide age range.