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Viral respiratory tract infection and exacerbations of asthma in adult patients.

The role of viral respiratory tract infections in acute exacerbations of asthma was studied prospectively in 31 patients with atopic asthma aged 15-56 years. Patients recorded symptom scores for asthma and peak expiratory flow rate daily for 11 months. In addition, they reported for detailed clinical, functional, and virological study every four weeks and as soon as possible after the onset of worsening asthma or symptoms suggesting a respiratory tract infection. Thirty viral identifications were made, of which 18 (60%) were associated with an exacerbation of asthma. Viral respiratory tract infection was identified in 18 (10%) of the 178 exacerbations of asthma, and in 10 (36%) of the 28 severe exacerbations. The frequency of viral identifications in 16 non-asthmatic, control subjects during the same period was similar. It is concluded that viral respiratory tract infections may cause or be associated with exacerbations of asthma in adults, and that they are an important factor in severe exacerbations.

Acute Disease↗

Soluble intercellular adhesion molecule-1 in sera of children with bronchial asthma exacerbation.

Previous studies have suggested that intercellular adhesion molecule-1 (ICAM-1; CD54) may be involved in the pathogenesis of asthma. In addition, a soluble form of intercellular adhesion molecule-1 (sICAM-1) has been detected in increased concentrations in the sera from adult patients with certain inflammatory, immune, or malignant diseases. To determine whether bronchial asthma exacerbation in children is associated with increased levels of serum sICAM-1 and to investigate the effect of the severity of exacerbation on these levels, the concentrations of sICAM-1 were measured in sera of 20 healthy control children and 45 asthmatic children (15 with mild, 15 with moderate, and 15 with severe asthma exacerbation) using an immunoenzymatic assay. Assessment of the severity of asthma exacerbation was based on clinical and physiological parameters. The mean (+/- SD) level of serum sICAM-1 for asthmatic children (390.0+/-108.3 ng/ml) was significantly higher than that for healthy (193.2+/-33.95 ng/ml; p = 0.000). We have also found a differential rise of serum sICAM-1 level which correlates well with the severity of asthma exacerbation. The elevated concentrations of serum sICAM-1 in acute bronchial asthma may reflect the extensive inflammatory response occurring in the airways during acute exacerbation of the disease with airway obstruction. The results of this study suggest that serum sICAM-1 is a promising serological marker of the severity of inflammation in bronchial asthma in children and it would not only facilitate staging of inflammation but also allow the monitoring of therapy and intervention.

Asthma↗

N-acetylcysteine reduces the exacerbation rate in patients with moderate to severe COPD.

OBJECTIVE: This study was performed to confirm the efficacy of a 6-month therapy with a formulation of N-acetylcysteine (NAC; 600 mg/day p.o.) on frequency and severity of exacerbations in patients suffering from chronic obstructive pulmonary disease (COPD). METHODS: One hundred sixty-nine patients attending five Italian centres were recruited in an open, randomized, controlled study. The patients were randomly allocated to standard therapy plus NAC 600 mg once a day or standard therapy alone over a 6-month period. At baseline, medical history was evaluated, and physical examination was performed; occurrence and severity of exacerbations and side effects of NAC were analyzed after 3 and 6 months. RESULTS: The results showed a decreased number of exacerbations (by 41%) in the group of patients treated with NAC and standard treatment: 46 patients had at least one exacerbation as compared with 63 patients of the group treated with standard therapy alone. Also the number of the patients with two or more exacerbations was lower in the NAC group (26%) than in the standard-therapy group (49%). The number of sick days was less (82) in the NAC group as compared with the standard-therapy group (155). There was a small but significant improvement in FEV(1) and MEF(50) in the NAC group. NAC once a day was well tolerated. There were no differences in the number of side effects reported in both groups. CONCLUSIONS: These data confirm results of previous studies which reported a reduction in the number of exacerbations in patients having moderate to severe COPD treated with the antioxidant NAC. Further, the once-daily formulation is well tolerated and is likely to improve patient compliance with the prescribed regimen.

Acetylcysteine↗

Factors associated with increased risk of exacerbation and hospital admission in a cohort of ambulatory COPD patients: a multiple logistic regression analysis. The EOLO Study Group.

BACKGROUND AND OBJECTIVE: The aim of this study was to develop and validate two models to estimate the probabilities of frequent exacerbations (more than 1 per year) and admissions for chronic obstructive pulmonary disease (COPD) that can be used in a primary care setting. METHODS: Information was obtained in a cross-sectional observational study on ambulatory COPD patients performed in 201 general practices located throughout Spain. The model for admissions included 713 cases, 499 for the developmental sample and 214 in the validation sample; the model for frequent exacerbations included 896 patients, 627 in the developmental sample and 269 in the validation model. Candidate variables to be included in both models were: age, sex, body mass index (BMI), FEV(1) as percent predicted [FEV(1 )(% pred.)], active smoking, chronic mucus hypersecretion (CMH) and significant comorbidity. RESULTS: The admission model contained 2 readily obtainable variables: comorbidity (OR = 1.97; CI 95% = 1. 24-3.14) and FEV(1)(% pred.) (OR = 0.72; 0.58-0.88, for every 10 units), and well calibrated in developmental and validation samples (goodness-of-fit tests: p = 0.989 and p = 0.720, respectively). The model for frequent exacerbations included 3 variables: age (OR = 1. 21; 1.01-1.44; for every 10 years of increasing age), FEV(1 )(% pred. ) (OR = 0.82; 0.70-0.96, for every 10 units) and CMH (OR = 1.54; 1. 11-2.14) and also well calibrated (p = 0.411 and p = 0.340 in the developmental and validation samples, respectively). CONCLUSIONS: Our results suggest that FEV(1) impairment explains part of the risk of frequent exacerbations and hospital admissions. Furthermore, CMH and increasing age are significantly associated with the risk of frequent exacerbations, but severity of exacerbations provoking hospital admissions is associated with the presence of significant comorbidity. These important and easily measurable variables contain valuable information for optimal management of ambulatory patients with COPD.

Age Factors↗

Airway eosinophilia in chronic bronchitis during exacerbations.

To examine the nature and the degree of airway inflammation in chronic bronchitis during exacerbations, bronchial biopsies and sputum were obtained in 11 subjects with chronic bronchitis examined during an exacerbation, and in 12 subjects with chronic bronchitis examined under baseline conditions. All subjects were nonatopic. Lobar bronchial biopsies were assessed using histochemical and immunohistochemical techniques, and sputum was examined for differential cell counts of leukocytes. Subjects with bronchitis during exacerbations had, on average, 30-fold more eosinophils in their bronchial biopsies than did those examined under baseline conditions (p < 0.001). Although to a lesser extent, the numbers of neutrophils (p < 0.01), T-lymphocytes (CD3) (p < 0.05), VLA-1-positive cells (p < 0.01), and TNF-alpha positive cells (p < 0.05) were also increased during exacerbations. By contrast, the T-lymphocyte subpopulations (CD4 and CD8) and the numbers of macrophages, mast cells, IL-2R-positive cells, and IL-1 beta-positive cells were similar in the two groups of subjects, as well as the percentages of ICAM-1- and E-selectin-positive vessels. Eosinophils were also increased in sputum of subjects with exacerbations when compared with those examined under baseline conditions (p < 0.05). In conclusion, exacerbations of chronic bronchitis are associated with a marked airway eosinophilia and with a milder increase in the number of neutrophils, activated T-lymphocytes, and TNF-alpha-positive cells in the bronchial mucosa.

Aged↗

Predictive factors of hospitalization for acute exacerbation in a series of 64 patients with chronic obstructive pulmonary disease.

Hospitalizations for acute exacerbation in patients with chronic obstructive pulmonary disease (COPD) have a great impact on health care expenditure. The aim of this study was to look at predictive factors of hospitalization for acute exacerbation in a group of patients with moderate to severe COPD. During the year 1994, we included 64 patients with COPD in this study. At inclusion, the patients being in a stable state, we performed a complete evaluation of their clinical, spirometric, gasometric, and pulmonary hemodynamic characteristics. All patients were followed during a period of at least 2.5 yr. We recorded the intervals free of hospitalization for exacerbation and realized an analysis of the proportional hazards not to be hospitalized using the Kaplan-Meier method. Univariate analysis using the log-rank test showed that the risk of being hospitalized was significantly increased in patients with COPD with a low body mass index (BMI <= 20 kg/m2, p = 0.015) and in patients with a limited 6-min walk distance (<= 367 m, p = 0. 045). But above all, the risk of hospitalization for acute exacerbation was significantly increased by gas exchange impairment and pulmonary hemodynamic worsening: PaO2 <= 65 mm Hg versus PaO2 > 65 mm Hg, p = 0.005; PaCO2 > 44 mm Hg versus PaCO2 <= 44 mm Hg, p = 0.005; and mean pulmonary artery pressure ( Ppa) at rest > 18 mm Hg versus Ppa <= 18 mm Hg, p = 0.0008. Neither age, nor the association of one or more comorbidities with COPD, nor the smoking habits had a significant impact on the risk of hospitalization in our study. Multivariate analysis showed that only PaCO2 and Ppa were independently related to the risk of hospitalization for acute exacerbation of COPD. We conclude that chronic hypercapnic respiratory insufficiency and pulmonary hypertension are predictive factors of hospitalization for acute exacerbation in COPD patients.

Aged↗

Comparison of nebulized budesonide and oral prednisolone with placebo in the treatment of acute exacerbations of chronic obstructive pulmonary disease: a randomized controlled trial.

Nebulized budesonide has been used successfully to treat acute asthma exacerbation, and we hypothesized that it could also be effective for exacerbations of chronic obstructive pulmonary disease (COPD). In this multicenter, double-blind, randomized, placebo-controlled trial, the efficacy of nebulized budesonide (Pulmicort Respules/Nebuamp), oral prednisolone, and placebo was compared in 199 patients with acute exacerbations of COPD requiring hospitalization. Patients received from randomization (H(0)) to 72 h (H(72)), 2 mg of budesonide every 6 h (n = 71), 30 mg of oral prednisolone every 12 h (n = 62), or placebo (n = 66). All received standard treatment, including nebulized beta(2)-agonists, ipratropium bromide, oral antibiotics, and supplemental oxygen. The mean change (95% confidence interval) in postbronchodilator FEV(1) from H(0) to H(72) was greater with active treatments than with placebo: budesonide versus placebo, 0.10 L (0.02 to 0.18 L); prednisolone versus placebo, 0.16 L (0.08 to 0.24 L). The difference in FEV(1) between budesonide and prednisolone was not significant, -0.06 L (-0.14 to 0.02 L). The occurrence of serious adverse events was similar for all groups. Budesonide had less systemic activity than prednisolone as indicated by a higher incidence of hyperglycemia observed with prednisolone. Both budesonide and prednisolone improved airflow in COPD patients with acute exacerbations when compared with placebo. Nebulized budesonide may be an alternative to oral prednisolone in the treatment of nonacidotic exacerbations of COPD but further studies should be done to evaluate its long-term impact on clinical outcomes after an initial episode of COPD exacerbation.

Acute Disease↗

Lymphocyte proliferative response to P6 of Haemophilus influenzae is associated with relative protection from exacerbations of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is characterized by periodic exacerbations, some of which are caused by nontypeable Haemophilus influenzae (NTHI). P6 is an outer membrane lipoprotein that is highly conserved among strains of NTHI. We hypothesized that lymphocytes from patients with COPD who have exacerbations due to NTHI have a decreased ability to recognize P6. The in vitro lymphocyte proliferative response to P6 in 36 patients with COPD and 12 healthy control subjects was studied. Ten patients who had exacerbations due to NTHI in the previous 12 months showed statistically significant lower proliferation to P6 (stimulation index, log transformed mean +/- standard error 0.82 +/- 0.17) compared with 26 patients who had no exacerbations due to NTHI in the previous 12 months (1.42 +/- 0.13) and to 12 healthy control subjects (1.61 +/- 0.16). These three groups had no significant difference in the lymphocyte proliferative response to tetanus toxoid. There was no difference in serum antibody levels to P6 in the two groups with COPD. These results indicate that decreased proliferation of T cells to P6 is associated with exacerbations of COPD and suggest that the ability of T cells to recognize P6 is associated with relative protection from exacerbations due to NTHI.

Aged↗

Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma.

The PREVIA study was designed to investigate the role of montelukast, a leukotriene receptor antagonist, in the prevention of viral-induced asthma exacerbations in children aged 2 to 5 years with a history of intermittent asthma symptoms. The study was a 12-month multicenter, double-blind, parallel-group study of patients with asthma exacerbations associated with respiratory infections and minimal symptoms between episodes. Patients were randomized to receive oral montelukast 4 or 5 mg (depending on age) (n = 278) or placebo (n = 271) once per day for 12 months. Caregivers recorded children's symptoms, beta-agonist use, and health care resource use in a diary card. Over 12 months of therapy, montelukast significantly reduced the rate of asthma exacerbations by 31.9% compared with placebo. The average rate of exacerbation episodes per patient was 1.60 episodes per year on montelukast compared with 2.34 episodes on placebo. Montelukast also delayed the median time to first exacerbation by approximately 2 months (p = 0.024), and the rate of inhaled corticosteroid courses (p = 0.027) compared with placebo. Montelukast effectively reduced asthma exacerbations in 2- to 5-year-old patients with intermittent asthma over 12 months of treatment and was generally well tolerated.

Acetates↗

Exacerbations and time spent outdoors in chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease have a progressive reduction in activity, although its time scale and the contribution of exacerbations are unknown. A rolling cohort of 147 patients (101 male; mean age, 88.5 years; and forced expiratory volume in 1 second as percent predicted, 38.4%) were monitored for a median of 1,044 days (interquartile range, 685 to 1,779) over an 8-year period starting in March 1996. Patients recorded any increase in daily respiratory symptoms and time spent outside their home. They completed the St. George's Respiratory Questionnaire yearly. They experienced 1,465 exacerbations and time outdoors decreased by -0.16 hours/day per year (p < 0.001). This decline was faster in frequent exacerbators (p = 0.011). Before exacerbation, the patients stayed indoors all day for 2.1 days/week (on any day 34.1% were at home), but for 5 weeks postexacerbation they spent 2.5 days/week at home (p < 0.001) (44.4% remaining at home at onset; p = 0.021). St. George's total, activity, and impact scores were independently associated with time outdoors (p < 0.005), but not with symptom score. In conclusion, time spent outside the home declines over time and acutely at exacerbation. Patients with frequent exacerbations are more likely to become housebound and need targeting in rehabilitation programs.

Activities of Daily Living↗

Lung mechanics and dyspnea during exacerbations of chronic obstructive pulmonary disease.

RATIONALE: Exacerbation of chronic obstructive pulmonary disease commonly causes hospitalization. The change in lung mechanics during exacerbation and its relationship to symptoms in spontaneously breathing individuals has not been described. OBJECTIVE: We hypothesized that changes in both airflow and lung volumes would occur during an exacerbation, but that only volume change would relate to symptomatic improvement. METHODS: Lung mechanics and resting dyspnea were recorded in 22 hospitalized patients during recovery from exacerbation. MEASUREMENTS: Spirometry, inspiratory capacity, respiratory system resistance and reactance, tidal breathing patterns, and expiratory flow limitation were recorded after nebulized bronchodilator therapy on the first 3 d after admission, at discharge, and 6 wk postadmission (Day 42). Prebronchodilator measurements were taken on Day 2, at discharge, and on Day 42. MAIN RESULTS: Postbronchodilator inspiratory capacity increased 0.23 +/- 0.07 L by discharge and 0.42 +/- 0.1 L by Day 42, FEV1 rose 0.09 +/- 0.04 and 0.2 +/- 0.05 L at discharge and Day 42, respectively, and FVC increased 0.21 +/- 0.08 and 0.47 +/- 0.09 L at discharge and Day 42 (all p < 0.05). Consistent reduction in dyspnea was seen as the exacerbation resolved. Respiratory system resistance, FEV1/FVC, and expiratory flow limitation were unchanged throughout, indicating that changes in lung volume rather than airflow resistance predominated. CONCLUSIONS: Improvement in operating lung volumes is the principal change seen as a chronic obstructive pulmonary disease exacerbation resolves and increase in inspiratory capacity is a useful guide to a reduction in dyspnea.

Aged↗

Systemic and upper and lower airway inflammation at exacerbation of chronic obstructive pulmonary disease.

RATIONALE: In addition to pulmonary involvement, stable chronic obstructive pulmonary disease (COPD) is associated with nasal and systemic inflammation. Although exacerbations of COPD are associated with increased pulmonary and systemic inflammation, determinants of the systemic response remain obscure, and nor is it known whether there is nasal involvement. OBJECTIVES: To investigate upper airway, lower airway, and systemic inflammation at exacerbation of COPD. METHODS: We sampled sputum, nasal wash, and serum from 41 exacerbations (East London cohort) for analysis of pathogenic microorganisms and inflammatory indices (sputum/nasal wash leukocytes, interleukin [IL]-6, IL-8, and myeloperoxidase; serum IL-6 and C-reactive protein). Values were compared with stable COPD. MEASUREMENTS AND MAIN RESULTS: Exacerbation of COPD is associated with greater nasal, sputum, and serum inflammation than the stable state. At exacerbation, inflammatory markers were highly correlated within nasal wash and serum (all r >/= 0.62, p < 0.001), but not sputum. The degree of upper airway inflammation correlated with the degree of lower airway inflammation (e.g., nasal wash/sputum myeloperoxidase; r = 0.50, p = 0.001). The degree of systemic inflammation correlated with the degree of lower airway inflammation (e.g., serum IL-6/sputum IL-8; r = 0.35, p = 0.026), and was greater in the presence of a sputum bacterial pathogen (29.0 g/dl C-reactive protein difference, p = 0.002). We did not find relationships between the upper airway and systemic compartments. CONCLUSIONS: Exacerbation of COPD is associated with pan-airway inflammation; the systemic inflammatory response is proportional to that occurring in the lower airway and greater in the presence of a bacterial pathogen.

Aged↗

Statistical treatment of exacerbations in therapeutic trials of chronic obstructive pulmonary disease.

Randomized trials and a meta-analysis suggesting that inhaled corticosteroids reduce exacerbation rates in patients with chronic obstructive pulmonary disease (COPD) show major discrepancies that may be due to different approaches to data analysis. These trials used statistical techniques that were either weighted or unweighted for follow-up time, with p values and confidence intervals estimated with or without accounting for between-patient variability in exacerbation rates. We illustrate the validity of these methods using data from a cohort of 5,454 patients with COPD structured to emulate a randomized trial. The "reference" group was defined as patients with a history of exacerbations before cohort entry (n=1,137), whereas the "treated" group included an equal number (n=1,137) of patients with no prior exacerbation. Random samples of 100 and 200 subjects were selected three times from each of two groups to further illustrate the variability in the findings. Exacerbations during follow-up were identified from prescriptions for systemic antibiotics. The correct rate ratio of 0.75 estimated by the weighted approach was underestimated as 0.57 by the unweighted approach. When the weighted approach did not, however, also account for between-patient variability, the p value was greatly underestimated (e.g., rate ratio, 0.79; p=0.0007 instead of p=0.12) and confidence intervals were much narrower than after properly accounting for this variability. In conclusion, the reports from randomized trials and the meta-analysis that inhaled corticosteroids reduce COPD exacerbation rates are the result of improper statistical analysis techniques. The only two studies that used the correct statistical approach found insignificant effects with these drugs.

Clinical Trials as Topic↗

IL4R alpha mutations are associated with asthma exacerbations and mast cell/IgE expression.

BACKGROUND: Severe asthma has been associated with severe exacerbations, lower lung function and greater tissue inflammation. Previous studies have suggested that mutations in interleukin-4 receptor alpha (IL4Ralpha) are associated with lower lung function, higher IgE, and a gain in receptor function. However, an effect on exacerbations and tissue inflammation has not been shown. HYPOTHESIS: Allelic substitutions in IL4Ralpha are associated with asthma exacerbations, lower lung function, and tissue inflammation, in particular to mast cells and IgE. METHODS: Two well-characterized cohorts of subjects with severe asthma were analyzed for five single nucleotide polymorphisms (SNPs) in IL4Ralpha. These polymorphisms were compared with the history of severe asthma exacerbations and lung function. In the primary (National Jewish) cohort, these polymorphisms were also compared with endobronchial tissue inflammatory cells and local IgE. RESULTS: In both cohorts, the presence of the minor alleles at E375A and Q551R, which were more common in African Americans, was associated with a history of severe exacerbations and lower lung function. In the National Jewish cohort, the C allele at E375A was associated with higher tissue mast cells and higher levels of IgE bound to mast cells. The significance for most of these associations remained when whites (the larger racial subgroup) were analyzed separately. CONCLUSIONS: SNPs in IL4Ralpha, which are more common in African Americans, are associated with severe asthma exacerbations, lower lung function, and increased mast cell-related tissue inflammation. Further studies of the impact of these mutations in African Americans and on receptor function are indicated.

Adult↗

Airway hyperreactivity in exacerbation of chronic asthma is independent of eosinophilic inflammation.

We have developed an animal model to investigate the mechanisms underlying an acute exacerbation of chronic asthma. Sensitized BALB/c mice were exposed to aerosolized ovalbumin, either as chronic low-level challenge (mass concentration approximately 3 mg/m(3)) for 4 wk, a single moderate-level challenge (approximately 30 mg/m(3)), or chronic low-level followed by single moderate-level challenge (the acute exacerbation group). Compared with animals receiving chronic challenge alone, mice in the acute exacerbation group exhibited a more marked inflammatory response, with involvement of intrapulmonary airways and lung parenchyma, and increased numbers of lymphocytes and eosinophils in bronchoalveolar lavage fluid. They also developed airway hyperreactivity (AHR) to methacholine, demonstrable as increased transpulmonary resistance and decreased compliance. This pattern of AHR was absent in chronically challenged animals, but was also present in animals given single moderate-level challenge. However, compared with animals receiving a single moderate-level challenge, inflammation and AHR were induced more rapidly in the acute exacerbation group. Eosinophil-deficient GATA1 Deltadbl mice exhibited undiminished AHR in the acute exacerbation model. We conclude that in mice with pre-existing airway lesions resembling mild chronic asthma, exposure to a moderately high concentration of inhaled antigen induces features of an acute exacerbation. The inflammatory response involves distal airways and is associated with a distinct pattern of AHR, which develops independent of the enhanced eosinophilic inflammation.

Animals↗

A teenager with severe asthma exacerbation following ibuprofen.

Aspirin-sensitive asthma, aspirin-intolerant asthma, aspirin- (or non-steroidal anti-inflammatory drug [NSAID]) exacerbated respiratory disease are terms for a disorder commonly described as affecting adults aged > 30y. With this perception, ibuprofen was administered for postoperative pain management to a 17-year-old boy with allergic rhinitis and previous severe asthma (at a time when well controlled), who then had a severe asthma exacerbation. Analysis of the literature in response to this case highlights four points: 1) NSAID-exacerbated asthma is not only a disorder of adults; it occurs in up to of 2% in asthmatic children, approaching probably 30% in older children with severe asthma and nasal disease. 2) The asthmatic reaction is dose-dependent and can occur with sub-therapeutic doses. Oral NSAID/aspirin challenge should be conducted in an environment where a severe asthma exacerbation can be appropriately managed. 3) The therapeutic use of non-selective [COX-1 preferential] NSAIDs should be avoided when sensitivity is known or suspected in adults and teenagers with severe asthma and chronic rhinosinusitis or nasal polyps. Use of these agents in younger children with mild episodic wheeze is probably safe. 4) Paracetamol use is probably safe, but aspirin-exacerbated respiratory disease may occur with clinical doses in a subgroup of aspirin-exacerbated respiratory disease patients. COX-2 selective inhibitors are probably safe, although this is controversial. Opioids and tramadol are suitable analgesic alternatives for patients with known or suspected susceptibility.

Adolescent↗

Effects of exacerbations and seasonality on exhaled nitric oxide in COPD.

Exhaled nitric oxide (eNO) appears to be associated with airway inflammation seen in chronic obstructive pulmonary disease (COPD). The present authors studied the effects of exacerbation, season, temperature and pollution on eNO. eNO was measured seasonally and at exacerbations in 79 outpatients suffering from COPD (mean forced expiratory volume in one second=42%). The effects of exacerbation symptoms, physiological and environmental parameters were analysed. Stable eNO levels were correlated positively with arterial oxygen tension. Median levels were found to be lower in smokers (5.3 ppb) than in ex- or nonsmokers (6.8 ppb). Levels were higher during October to December (6.9 ppb) than in April to June (4.6 ppb). Levels were also higher during 68 exacerbations in 38 patients (7.4 ppb) than in stable conditions (5.4 ppb), independent of the effects of smoking. The rise in eNO was greater in exacerbations that were associated with colds, a sore throat or dyspnoea combined with a cold. In conclusion, exhaled nitric oxide levels were higher in colder weather and in the autumn, perhaps related to the increased prevalence of viral infection at this time of year. The levels were lower in more severe chronic obstructive pulmonary disease. Exhaled nitric oxide levels were raised at the onset of exacerbation, particularly in the presence of a cold.

Age Distribution↗

Determining asthma treatment by monitoring sputum cell counts: effect on exacerbations.

One important goal of asthma treatment is to reduce exacerbations. The current authors investigated if the use of sputum cell counts to guide treatment would achieve this goal. A total of 117 adults with asthma were entered into a multicentre, randomised, parallel group-effectiveness study for two treatment strategies over a 2-yr period. In one strategy (the clinical strategy: CS) treatment was based on symptoms and spirometry. In the other (the sputum strategy: SS) sputum cell counts were used to guide corticosteroid therapy to keep eosinophils 250 microg, and was due to fewer eosinophilic exacerbations. The cumulative dose of corticosteroid during the trial was similar in both groups. Monitoring sputum cell counts was found to benefit patients with moderate-to-severe asthma by reducing the number of eosinophilic exacerbations and by reducing the severity of both eosinophilic and noneosinophilic exacerbations without increasing the total corticosteroid dose. It had no influence on the frequency of noneosinophilic exacerbations, which were the most common exacerbations.

Adult↗