Differential flow analysis of exhaled nitric oxide in patients with asthma of differing severity

BACKGROUND: The majority of asthmatic patients achieve control of their illness; others do not. It is therefore crucial to validate/develop strategies that help the clinician monitor the disease, improving the response to treatment. METHODS: We have quantified the inflammation in central and peripheral airways by measuring exhaled nitric oxide (NO) at multiple exhalation flows in 56 asthmatics at different levels of severity (mild, n = 10; moderate stable, n = 17; moderate during exacerbation, n = 11; severe, n = 18, 7 of whom were receiving oral corticosteroids) and 18 healthy control subjects. The reproducibility of the measurement was also assessed. RESULTS: Bronchial NO (Jno) in patients with mild asthma (2,363 +/- 330 pL/s) [mean +/- SD] was higher than in patients with moderate stable asthma (1,300 +/- 59 pL/s, p < 0.0005), in patients with severe asthma receiving inhaled corticosteroids (ICS) [1,015 +/- 67 pL/s, p < 0.0005], and healthy control subjects (721 +/- 22 pL/s, p < 0.0001). There were no differences between Jno in patients with mild asthma compared to patients with severe asthma receiving ICS and oral corticosteroids (2,225 +/- 246 pL/s). Patients with exacerbations showed a higher Jno (3,475 +/- 368.9 pL/s, p < 0.05) compared to the other groups. Alveolar NO was higher in patients with severe asthma receiving oral corticosteroids (3.0 +/- 0.1 parts per billion [ppb], p < 0.0001) than in the other groups but was not significantly higher than in patients with moderate asthma during exacerbation (2.8 +/- 0.3 ppb). No differences were seen in NO diffusion levels between the different asthma groups. All the measurements were highly reproducible and free of day-to-day and diurnal variations. CONCLUSIONS: Differential flow analysis of exhaled NO provides additional information about the site of inflammation in asthma and may be useful in assessing the response of peripheral inflammation to therapy.     

Portable exhaled nitric oxide as a screening tool for asthma in young adults during pollen season

BACKGROUND: The fraction of exhaled NO (FeNO) is valuable for the follow-up of asthmatic patients. However, its usefulness as a screening tool for asthma is not established. METHODS: We screened a population of 961 university students with a modified European Community Respiratory Health Survey questionnaire that has been previously used for the screening of respiratory symptoms related to asthma. All subjects with a positive answer to at least one question (n = 149) were submitted to FeNO measurement with a portable nitric oxide analyzer. Subsequently, they were submitted to spirometry and evaluated by a physician blinded to FeNO measurements. Seventy students with no respiratory symptoms served as control subjects. RESULTS: Asthma was diagnosed in 63 subjects, and allergic rhinitis was diagnosed in 57 subjects. Asthmatics presented higher FeNO values than control subjects (median, 20 parts per billion [ppb]; interquartile range, 14 to 31 ppb; vs median, 11 ppb; interquartile range, 7 to 13 ppb, respectively; p < 0.0001), whereas they did not differ from patients with allergic rhinitis (median, 17 ppb; interquartile range, 12 to 23 ppb; p = 0.28). FeNO values > 19 ppb presented 85.2% specificity and 52.4% sensitivity for the diagnosis of asthma (area under the curve [AUC], 0.723). The diagnostic performance of FeNO was better in nonsmokers (AUC, 0.805), yet FeNO values > 25 ppb were characterized by specificity > 90% for the diagnosis of asthma both in smokers and in nonsmokers. However, FeNO was not a good marker for the differentiation between asthma and allergic rhinitis. CONCLUSIONS: FeNO measurement with a portable analyzer is useful for the screening for asthma in young adults. Significant confounding factors are allergic rhinitis and current smoking.     

Portable exhaled nitric oxide measurement: Comparison with the "gold standard" technique

Background:The measurement of fractional exhaled nitric oxide (FENO) can assist in the diagnosis of asthma and may also act as a useful surrogate inflammatory marker on which to base treatment decisions in asthma management algorithms. Until recently, this technique was confined to research facilities and secondary care institutions. A portable nitric oxide analyzer (MINO; Aerocrine AB; Smidesvägen, Sweden) has been developed, but few data exist comparing this device with established, larger laboratory-based analyzers (NIOX; Aerocrine AB).Methods:A total of 101 asthmatic patients (64 treated with regular inhaled corticosteroids) and 50 healthy volunteers had simultaneous FENO measurements undertaken using NIOX and MINO devices.Results:In both asthmatic patients and healthy volunteers, there was a good correlation between the measurements obtained using each device (r= 0.94 and 0.96, respectively). Altman-Bland plots confirmed this agreement. Receiver operating characteristic curves discriminating asthmatic patients from healthy volunteers obtained using the NIOX and MINO showed a sensitivity of 83.2% and a specificity of 72% using cutoff values of 13 and 12.5 parts per billion, respectively.Conclusion:FENO values obtained using a portable analyzer correlate well with those obtained using an established laboratory analyzer and can be used to discriminate asthmatic from nonasthmatic patients. This may facilitate the measurement of asthmatic airway inflammation in primary care.     

The use of fraction of exhaled nitric oxide in pulmonary practice

The measurement of the fractional concentration of exhaled nitric oxide (FeNO) is a convenient, noninvasive, point-of-service office test for airway inflammation. The first half of this practice management review presents the methodological, interpretative, and clinical applications of FeNO. The second half discusses practical management issues, including current and future technology, equipment specifications, US Food and Drug Administration regulations, cost, current procedural terminology coding, and reimbursement. The measurement of FeNO is helpful in the diagnosis of asthma. It is predictive of a response to inhaled corticosteroids (ICSs). Monitoring FeNO is useful in maintaining asthma control by allowing the assessment of adherence to medication and dose titration of ICSs. An elevated level of FeNO is predictive of asthma relapse following corticosteroid withdrawal especially in children. The advances in technology, ease of use, and clinical utility will lead to greater availability, acceptance, and routine application in the care of asthma.     

Fraction of exhaled nitric oxide at 50 mL/s: reference values for adult lifelong never-smokers

BACKGROUND: The measurement of fractional exhaled nitric oxide (FENO) is used as a marker of airway inflammation. The aim of this study was to establish reference values of FENO for adults. METHODS: FENO at a flow rate of 50 mL/s was analyzed in 3,376 adults using a chemiluminescence analyzer according to American Thoracic Society/European Respiratory Society guidelines. Blood samples were analyzed, and atopy was defined as the presence of specific IgE. All subjects responded to a respiratory questionnaire. Those who had never smoked (n = 1,803) were selected for this study. After the exclusion of subjects with physician-diagnosed asthma, asthma symptoms, ever wheezing, dry cough, or use of inhaled steroids, 1,131 healthy never-smokers remained, including 845 nonatopic and 286 atopic subjects. RESULTS: Based on multiple regression modeling, we propose the following reference equation for healthy never-smoking adults: Ln(FENO) = 0.057 + 0.013 x height (in centimeters) + 0.0088 x age (in years). The residual SD was 0.51, and the explanatory value was 9%. In a model, based on nonatopic subjects alone, the reference equation obtained was slightly different, as follows: Ln(FENO) = -0.0026 + 0.013 x height (in centimeters) + 0.010 x age (in years). The residual SD for this equation was 0.48, and the explanatory value was 11%. CONCLUSIONS: Normal values of FENO for adults may be predicted on the basis of age and height. However, as the reference equations only account for about 9 to 11% of the variation, the most important information that could be extracted from the study is that the upper limits of FENO range from 24.0 to 54.0 parts per billion, depending on age and height.     

Normal bronchial blood flow in COPD is unaffected by inhaled corticosteroids and correlates with exhaled nitric oxide

BACKGROUND: In COPD patients, there is reduced vascularity and inflammation of the bronchi, which may have opposite effects on bronchial blood flow (QAW). We studied the relationship of QAW with the fraction of exhaled nitric oxide (FENO), which is a potent vasodilator. We also investigated the vascular response to budesonide and a beta(2)-agonist. METHODS: We measured QAW in 17 patients with COPD (mean [+/- SEM] age, 67 +/- 3 years; 10 male patients; mean FEV(1), 57 +/- 3% predicted; mean FEV(1)/FVC ratio, 54 +/- 4%), all of whom were ex-smokers, and in 16 age-matched nonsmoking volunteers (mean age, 64 +/- 4 years) and compared this to FENO. QAW was measured using the acetylene dilution method. RESULTS: Mean QAW was similar in patients with COPD (34.29 +/- 1.09 microL/mL/min) compared to healthy subjects (35.50 +/- 1.74 microL/mL/min; p > 0.05) and was not affected by long-term treatment (35.89 +/- 1.63 microL/mL/min) or short-term treatment (32.50 +/- 1.24 microL/mL/min; p < 0.05) with inhaled budesonide. QAW positively correlated with the diffusion of carbon monoxide (ie, carbon monoxide transfer coefficient: r = 0.74; p < 0.05). FENO levels were mildly elevated in steroid-treated patients (10.89 +/- 0.87 parts per billion [ppb]) and untreated patients (9.40 +/- 0.86 ppb) compared to the control group (8.22 +/- 0.57 ppb; p < 0.05) and were correlated with QAW (r = 0.6; p < 0.05). Ten minutes after the inhalation of 200 microg of albuterol, QAW was more elevated in healthy control subjects (59.33 +/- 2.40 microL/mL/min) compared to COPD patients (38.00 +/- 0.58 microL/mL/min; p < 0.05), indicating that COPD patients may have a reduced bronchial vascular reactivity. CONCLUSIONS: QAW is normal in COPD patients and is not affected by therapy with inhaled corticosteroids or beta(2)-agonists. In addition, QAW correlates with levels of FENO, which may have a regulatory role.     

FEV1 performance among patients with acute asthma: results from a multicenter clinical trial

OBJECTIVE: To determine the ability of patients seen for acute asthma exacerbations in the emergency department (ED) to perform good-quality FEV(1) measurements. METHODS: Investigators from 20 EDs were trained to perform spirometry testing as part of a clinical trial that included standardized equipment with special software-directed prompts. Spirometry was done on ED arrival and 30 min, 1 h, 2 h, and 4 h later, and during follow-up outpatient visits. MEASUREMENTS: Study performance criteria differed from American Thoracic Society (ATS) guidelines because of the population acuity and severity of illness as follows: ability to obtain acceptable FEV(1) measures (defined as two or more efforts with forced expiratory times >/= 2 s and time to peak flow < 120 ms or back-extrapolated volume < 5% of the FVC) and reproducibility criteria (two highest acceptable FEV(1) values within 10% of each other). RESULTS: Of the 620 patients (age range, 12 to 65 years), > 90% met study acceptability criteria on ED arrival and 74% met study reproducibility criteria. Mean initial FEV(1) was 38% of predicted. Spirometry quality improved over time; by 1 h, 90% of patients met study acceptability and reproducibility criteria. Patients with severe airway obstruction (FEV(1) < 25% of predicted) were initially less likely to meet quality goals, but this improved with time. The site was also an independent predictor of quality. CONCLUSION: When staff are well trained and prompt feedback regarding adequacy of efforts is given, modified ATS performance goals for FEV(1) tests can be met from most acutely ill adolescent and adult asthmatics, even within the first hour of evaluation and treatment for an asthma exacerbation.     

Absence of relationships between tuberculin responses and development of adult asthma with rhinitis and atopy

OBJECTIVE: To investigate the relationship between tuberculin skin responses and the development of adult asthma, rhinitis, and atopy. METHODS: Two hundred fourteen patients with mild-to-moderate asthma accompanied with rhinitis and 220 normal volunteers underwent a medical history, chest radiography, allergen skin-prick testing (SPT), bovine Mycobacterium tuberculosis vaccine (BCG) scar identification, purified protein derivative (PPD) tuberculin skin testing, serum-total and serum-specific IgE measurements, and bronchial provocation (provocative dose of histamine causing a 20% fall in FEV(1) [PD(20)]). RESULTS: Thirty-one normal volunteers (14.1%) and 168 asthma-rhinitis subjects (78.5%) had one or more positive skin test results (p < 0.0001). Neither the presence of a BCG scar nor a history of BCG vaccination had a significant effect on atopy in either group. The rate of PPD positivity had no statistical difference between atopy and nonatopy in both groups. In multivariate logistic regression analysis, the odds ratio for tuberculin reactivity was not related to the level of serum-total IgE nor to the level of serum-specific IgE to Dermatophagoides pteronyssinus (DP) and Dermatophagoides farinae (DF), skin response to DP and DF, and PD(20). Overall, no significant correlations were found between tuberculin skin reactivity and log serum-total IgE or PD(20). CONCLUSION: There is no relationship between history of tuberculosis infection, tuberculin responses, and development of adult bronchial asthma, allergic rhinitis, and atopy. Our study suggests that the protection provided by intradermal BCG vaccination in infants to prevent atopic diseases may be limited in early childhood, when a substantial memory of cellular immune modulation still exists.     

Airway nitric oxide in patients with cystic fibrosis is associated with pancreatic function, Pseudomonas infection, and polyunsaturated fatty acids

BACKGROUND: Airway nitric oxide (NO) is low or normal in cystic fibrosis (CF) patients. This may affect bacterial status since NO has antimicrobial properties. Arachidonic acid (AA), which is increased in the serum and airways of CF patients, has been shown to reduce NO levels. The aim of this study was to investigate whether airway NO level correlates with genotype and pancreatic function, and whether low airway NO level is associated with bacterial infection and increased serum AA level in CF patients. METHOD: Nasal NO (nNO) and exhaled NO (eNO) were measured according to the European Respiratory Society/American Thoracic Society standard in 59 CF patients aged 7 to 55 years, 80% of whom were pancreatic insufficient (PI) and 51% were chronically infected with Pseudomonas aeruginosa. RESULTS: PI CF patients had significantly lower nNO levels than pancreatic-sufficient (PS) patients. Airway NO level did not correlate with lung function or inflammatory parameters. PI patients chronically infected with P aeruginosa had significantly lower nNO levels than noninfected PI patients. nNO level correlated inversely with the AA/docosahexaenoic acid ratio, and eNO with the essential fatty acid (FA) deficiency index, which is the ratio between mead acid and AA. CONCLUSIONS: CF patients with PI, which is associated with more severe genotypes, had lower airway NO levels than patients with PS. Low NO level was correlated to chronic P aeruginosa infection, and an association was found between airway NO level and the abnormal serum phospholipid FA pattern.     

Hemodynamic effects of sildenafil in patients with congestive heart failure and pulmonary hypertension: combined administration with inhaled nitric oxide

STUDY OBJECTIVES: In patients with pulmonary hypertension (PH) secondary to congestive heart failure, inhaled nitric oxide (NO) increases pulmonary vascular smooth-muscle intracellular cyclic guanosine monophosphate (cGMP) concentration, thereby decreasing pulmonary vascular resistance (PVR) and increasing cardiac index (CI). However, these beneficial effects of inhaled NO are limited in magnitude and duration, at least in part due to cGMP hydrolysis by the type 5 isoform of phosphodiesterase (PDE5). The goal of this study was to determine the acute pulmonary and systemic hemodynamic effects of the selective PDE5 inhibitor, sildenafil, administered alone or in combination with inhaled NO in patients with congestive heart failure and PH. DESIGN: Single center, case series, pharmacohemodynamic study. SETTING: Cardiac catheterization laboratory of a tertiary care academic teaching hospital. PATIENTS: We studied 11 patients with left ventricular systolic dysfunction due to coronary artery disease or idiopathic dilated cardiomyopathy who had PH. INTERVENTIONS: We administered oral sildenafil (50 mg), inhaled NO (80 ppm), and the combination of sildenafil and inhaled NO during right-heart and micromanometer left-heart catheterization. MEASUREMENTS AND RESULTS: Sildenafil administered alone decreased mean pulmonary artery pressure by 12 +/- 5%, PVR by 12 +/- 5%, systemic vascular resistance (SVR) by 13 +/- 6%, and pulmonary capillary wedge pressure by 12 +/- 7%, and increased CI by 14 +/- 5% (all p < 0.05) [+/- SEM]. The combination of inhaled NO and sildenafil decreased PVR by 50 +/- 4%, decreased SVR by 24 +/- 3%, and increased CI by 30 +/- 4% (all p < 0.01). These effects were greater than those observed with either agent alone (p < 0.05). In addition, sildenafil prolonged the pulmonary vasodilator effect of inhaled NO. Administration of sildenafil alone or in combination with inhaled NO did not change systemic arterial pressure or indexes of myocardial systolic or diastolic function. CONCLUSIONS: PDE5 inhibition with sildenafil improves cardiac output by balanced pulmonary and systemic vasodilation, and augments and prolongs the hemodynamic effects of inhaled NO in patients with chronic congestive heart failure and PH.     

Diagnostic tests for asthma in firefighters

BACKGROUND: Subjects with asthma do not meet medical requirements for professions such as firefighting. OBJECTIVE: To prospectively determine the diagnostic value of respiratory symptoms and various tests used in the assessment of asthma in a cohort of firefighters. METHODS: A questionnaire, spirometry, direct and indirect airway challenge tests, exhaled nitric oxide, and skin-prick tests were administered prospectively to 101 of 107 firefighters employed in Basel, Switzerland. Asthma was defined as the combination of respiratory symptoms with airway hyperresponsiveness. RESULTS: Six of 101 firefighters (6%) had physician-diagnosed asthma, which could be confirmed in 4 firefighters. In contrast, asthma was diagnosed in 14% (14 of 101 firefighters). Wheezing was the most sensitive symptom for the diagnosis of asthma (sensitivity, 78%; specificity, 93%). Other respiratory symptoms showed a higher specificity than wheezing but a markedly lower sensitivity. Bronchial airway challenge with mannitol was the most sensitive (92%) and specific (97%) diagnostic test for asthma. Using a cutoff point of 47 parts per billion, nitric oxide had a similar specificity (96%) but lower sensitivity (42%) compared to the direct (methacholine) and indirect (mannitol) airway challenge tests. CONCLUSION: Asthma was considerably underdiagnosed in firefighters. The combination of a structured symptom questionnaire with a bronchial challenge test allows to identify patients with asthma and should routinely be used in the assessment of active firefighters and may be of help when evaluating candidates for this profession.     

Nasal nitric oxide in atypical primary ciliary dyskinesia

BACKGROUND: Atypical cases of primary ciliary dyskinesia (PCD) may present with minimal transmission electron microscopy (TEM) defects. The diagnostic role of nasal nitric oxide (nNO) levels was evaluated in those patients. METHODS: Sixty-four children with recurrent pneumonia were studied with ciliary motion analysis, TEM, and nNO. RESULTS: Investigations indicated PCD in 12 patients, secondary ciliary dyskinesia (SCD) in 50 patients, and normal results in 2 patients. In 4 of 50 children with SCD, atypical PCD was considered possible. The mean (+/- SD) nNO was 130 +/- 46.95 parts per billion in children affected by PCD, 127.79 +/- 68.58 parts per billion in atypical patients, and 760 +/- 221 parts per billion in children with SCD. Three to 5 months later, the nNO level was 132.75 +/- 55.76 parts per billion in children with atypical disease and 778.00 +/- 197 parts per billion in children with SCD. CONCLUSION: Low levels of nNO may help to identify patients with atypical PCD.     

Exhaled nitric oxide concentration is affected by age, height, and race in healthy 9- to 12-year-old children

BACKGROUND: The fractional concentration of exhaled nitric oxide (Feno) is a useful indicator of airway inflammation in children and adults with asthma. METHODS: We determined the range of Feno concentrations and the factors affecting it in a large sample of healthy school children attending grades 4 through 6, in Windsor, ON, Canada. RESULTS: Feno was measured in 657 children between 9.1 and 12.9 years of age. The range of Feno concentrations in healthy school children was 12.7 parts per billion (ppb) [95% confidence interval (CI), 11.8 to 13.7 ppb] in whites and 22.8 ppb [95% CI, 17.9 to 27.7 ppb] in Asian-Canadian children (p < 0.001). Feno values also appeared to be higher in African-Canadian children than in whites, although the CI was wide because of the small number of African-Canadian children sampled. Feno rose slightly but significantly with age (p = 0.007) and with height (p = 0.023). Body mass index and gender did not significantly alter the measured Feno. FVC had a nonsignificant effect on Feno. Participation in physical activity during the same day had a borderline-significant effect on measured Feno, but a reported history of a respiratory tract infection in the preceding 2 weeks did not. CONCLUSIONS: Feno concentrations in healthy school-aged children appeared to be affected by race, and, to a lesser extent, by age and height. These factors should be taken into consideration when interpreting clinical results.     

Occupational asthma and work-exacerbated asthma: factors associated with time to diagnostic steps

BACKGROUND: Little is known regarding the factors associated with the times for patients' first physician visit, the first physician suspicion of work-related asthma (WRA), and final diagnosis after the onset of WRA symptoms. This study examined individual and work-related factors that are associated with longer times to these diagnostic milestones among groups with occupational asthma (OA) and work-exacerbated asthma (WEA). METHOD: Suspected WRA cases were identified from an occupational lung disease clinic and claimants to the Ontario Workplace Safety and Insurance Board (100 patients each). Questionnaire administration and chart review were undertaken. RESULTS: Eighty participants were classified as having sensitizer-induced OA and 87 as having WEA. For the OA group, the risk factors for delay included male sex, being unmarried, low education, and lack of awareness of association of symptoms with work. Other factors included older age, being the sole income earner, and lack of knowledge of the Workplace Hazardous Materials Information System program. For WEA, lower household income, lower education, absence of a health-and-safety program at work, absence of a union, and lack of awareness of OA and of agents at work that could affect asthma significantly increased the time to diagnostic milestones. CONCLUSIONS: Different factors affect the diagnostic milestones for OA and WEA. Findings suggest a need for educational programs for workers who are at risk of OA and WEA and a need for further primary care physician education on WRA.     

Alveolar nitric oxide and effect of deep inspiration during methacholine challenge

STUDY OBJECTIVES: To assess whether the dual anatomic origin of exhaled nitric oxide (NO), namely alveolar and bronchial, could explain the link between exhaled NO and airway responsiveness, and could participate in the bronchodilatory effect of deep inspiration (DI) that may be evidenced during methacholine challenge. DESIGN AND SETTING: Prospective study in a laboratory performing pulmonary function tests of an academic hospital. PATIENTS AND INTERVENTIONS: Patients underwent multiple flow analysis of exhaled NO, allowing calculation of total maximum airway NO flux (J'awno) and NO concentration of expansible compartment (CAno), and received a cumulative methacholine dose of 2,000 microg. DI effect was assessed by continuous measurement of the resistance of respiratory system using the forced oscillation technique before and after DI. RESULTS: In a first phase involving 23 patients, a positive correlation between log values of J'awno and CAno was demonstrated with the degree of airway responsiveness (percentage of FEV(1) decrease). In a second phase involving 38 patients, only log CAno was correlated with responsiveness, and no significant relationship was demonstrated between J'awno or CAno and the effect of DI. Patients with smaller airways and/or distal airflow limitation exhibited a constrictive response to DI. CONCLUSION: Airway responsiveness is mainly associated with an increase in distal origin of NO output, and no relationship between exhaled NO and the effect of DI was evidenced.     

Lung diffusing capacity for nitric oxide and carbon monoxide: dependence on breath-hold time

BACKGROUND: The combined measurement of diffusing capacity of the lung for nitric oxide (Dlno) and diffusing capacity of the lung for carbon monoxide (Dlco) is a simple, noninvasive tool, but methodologic factors might influence results and reproducibility. We thus quantified the influence of breath-hold time on Dlco and Dlno in subjects with or without airway disease. METHODS: Simultaneous single-breath measurements of Dlco and Dlno were performed in 10 patients with cystic fibrosis (CF) [mean +/- SD age, 33 +/- 9 years; FEV(1), 69 +/- 28% of predicted] and 10 healthy subjects (age, 31 +/- 9 years; FEV(1), 108 +/- 8% of predicted), using the Masterscreen PFT (Viasys/Jaeger; H?chberg, Germany), with 45 ppm of inspired nitric oxide (NO), and breath-hold times of 4 s, 6 s, 8 s, and 10 s. The last two of three consecutive measurements were used for analysis. RESULTS: In healthy subjects but not patients with CF, Dlno, and Dlco differed significantly (p < 0.05 each) between breath-hold times. Differences primarily occurred at 4 s and 10 s, while at 6 s and 8 s alveolar volume (VA), Dlno, Dlco, and Dlno/Dlco were similar. Variability of consecutive measurements (either three or the last two measurements) did not depend on breath-hold time. At 8 s, mean variabilities of Dlno and Dlco in healthy subjects were 4.9% and 2.5%, respectively, and 4.2% and 3.2% at 6 s. At 8 s, mean variabilities of Dlno and Dlco in CF patients were 4.4% and 1.9%, and 7.4% and 3.3% at 6 s. CONCLUSIONS: Single-breath determinations of dlno and dlco showed no difference between breath-hold times of 6 s and 8 s in subjects with or without airway obstruction, and reproducibility was acceptable. Standardization of breath-hold time for Dlno measurements seems important for clinical and research comparisons.     

Differences in airway cytokine profile in severe asthma compared to moderate asthma

BACKGROUND: Some studies of severe asthma suggest that persistence or alteration in the pattern of inflammation may be associated with the severity of the disease. Whether there are differences in the expression of the principal cytokines and chemokines relevant to eosinophilic and neutrophilic inflammation in the airway tissues of severe compared to moderate asthmatics has not been determined. The aim of this study was to compare the patterns of expression of representative T-helper (Th) type 1 (interferon [IFN]-gamma) and Th-2 cytokines (interleukin [IL]-4, IL-5) and the neutrophil- and eosinophil-associated chemokines (IL-8 and eotaxin) in the airway tissues of patients with severe and moderate asthma. METHODS: Subjects with severe asthma (n = 24) and a comparison moderate asthma group (n = 26) were assessed using spirometry, induced sputum, exhaled nitric oxide, and bronchial biopsy. The expression of proteins of interest in the epithelium and subepithelium of the airway wall was examined by immunocytochemistry. RESULTS: Subjects with severe asthma were more symptomatic, had a lower FEV(1), and had more sputum neutrophilia (p = 0.007) and eosinophilia (p = 0.001). Exhaled nitric oxide was similar between groups. IL-8 and IFN-gamma expression were increased and IL-4 expression was decreased in severe asthma compared to moderate disease (p < 0.001 for each comparison). Eotaxin and IL-5 expression did not differ between the groups. CONCLUSION: Patients with severe asthma have increases in neutrophils and eosinophils in the sputum, and differ in airway cytokine/chemokine expression from moderate asthmatics. Excess neutrophilia may be explained by increased expression of IL-8, but differences in eosinophilia do not appear to be associated with IL-5 and eotaxin expression.