BACKGROUND:

Proximity to major roads is reported to be associated with asthma and airway hyper-responsiveness in children. Similar studies using objective measurements in adults are not available in Canada.

OBJECTIVE:

To test the hypothesis that adult asthmatic patients who live close to major roads and highways in an urban environment are at a risk of moderate to severe airway hyper-responsiveness.

METHODS:

Airway responsiveness was determined using methacholine bronchial provocation (PC20) tests in a cohort of 2625 patients who attended an outpatient clinic in Hamilton, Ontario. Patient addresses were geocoded in a geographic information system to determine proximity to major roads and highways. Multivariate linear and multinomial regression analyses were used to assess whether proximity to roads was a risk factor for airway hyper-responsiveness as measured by PC20 methacholine.

RESULTS:

Patients who lived within 200 m of a major road had increased odds (OR 1.38 [95% CI 1.04 to 1.85]) of having moderate airway hyper-responsiveness (0.25 mg/mL 16 mg/mL). Spatial analysis also revealed that the majority of patients with severe airway hyper-responsiveness lived within the urban core of the city while those with moderate to mild hyper-responsiveness were also dispersed in rural areas.

CONCLUSIONS:

In an adult population of patients attending an outpatient respiratory clinic in Hamilton, living close to major roadways was associated with an increased risk of moderate airway hyper-responsiveness. This correlation suggests that exposure to traffic emissions may provoke the pathology of airway hyper-responsiveness leading to variable airflow obstruction.

The present case series describes four patients with asthma, airway hyper-responsiveness and neutrophilic bronchitis who harboured abnormal cystic fibrosis transmembrance conductance regulator (CFTR) gene mutations. It serves both to alert clinicians to consider CFTR-related disease in both young and elderly patients with persistent neutrophilic bronchitis, and to highlight the potential utility of future genetic testing for CFTR abnormalities in patients with asthma and recurrent bronchitis or pansinusitis, and the role of nebulized hypertonic saline as a therapeutic option in these patients.

The immunological and clinical parameters that are associated with asthma remission are poorly understood. The cytokine and local mediator changes associated with the resolution of asthma symptoms were examined in three groups of subjects 12–18 years of age (n = 15 in each group): (a) continuing asthma group (CA) who had persistent symptoms since early childhood, (b) an age, sex and atopic status-matched group who had persistent symptoms in early childhood but in whom these had resolved (RA), and (c) a non-atopic, non-asthmatic control group. Clinical parameters, sputum cell counts, peripheral blood mononuclear cell (PBMC) cytokine production and activation marker expression were determined. All of the CA had methacholine airway hyperresponsiveness compared with only half of the RA subjects. The CA showed elevated numbers of eosinophils and increased ECP and IL-5 in sputum, which were not observed in the RA. PBMC cytokine studies revealed increased production of the type 1 cytokines IL-12, IFN-γ and TNF-α in the CA group compared with the RA group, under a range of activation conditions, however, the production of IL-4 and IL-5 were unchanged. These findings suggest that decreased type 1 cytokine expression as well as decreased eosinophilic inflammation is associated with the resolution of asthma symptoms.

BACKGROUND:

Noneosinophilic asthma has been regarded as a distinct phenotype characterized by a poor response to inhaled corticosteroids (ICS).

OBJECTIVE:

To determine whether noneosinophilic, steroid-naive asthmatic subjects show an improvement in asthma control, asthma symptoms and spirometry after four weeks of treatment with ICS, and whether they further benefit from the addition of a long-acting beta-2 agonists to ICS.

METHODS:

A randomized, double-blind, placebo-controlled, multicentre study comparing the efficacy of placebo versus inhaled fluticasone propionate 250 μg twice daily for four weeks in mildly uncontrolled, steroid-naive asthmatic subjects with a sputum eosinophil count ≤2%. This was followed by an open-label, four-week treatment period with fluticasone propionate 250 μg/salmeterol 50 μg, twice daily for all subjects.

RESULTS:

After four weeks of double-blind treatment, there was a statistically significant and clinically relevant improvement in the mean (± SD) Asthma Control Questionnaire score in the ICS-treated group (n=6) (decrease of 1.0±0.5) compared with the placebo group (n=6) (decrease of 0.09±0.4) (P=0.008). Forced expiratory volume in 1 s declined in the placebo group (−0.2±0.2 L) and did not change in the ICS group (0.04±0.1 L) after four weeks of treatment (P=0.02). The open-label treatment with fluticasone propionate 250 μg/salmeterol 50 μg did not produce additional improvements in those who were previously treated for four weeks with inhaled fluticasone alone.

CONCLUSION:

A clinically important and statistically significant response to ICS was observed in mildly uncontrolled noneosinophilic asthmatic subjects.

The clinical utility of using quantitative cell counts in sputum for the evaluation of obstructive airway diseases has been previously demonstrated. Although neutrophil counts and activation products have been reported to increase in the sputum of patients with bronchiectasis, it is not known whether these are predictive parameters. This study aimed to assess the accuracy and measurement properties of quantitative sputum cell counts to identify bronchiectasis detected by high-resolution computed tomography scans of the thorax. If validated in larger prospective studies, these parameters may decrease the need for high-resolution scans to detect bronchiectasis and limit radiation exposure.

BACKGROUND:

Quantitative cell counts in sputum provide an accurate assessment of the type and severity of bronchitis.

OBJECTIVE:

To examine whether sputum cell counts could identify bronchiectasis in patients with recurrent bronchitis.

METHODS:

A retrospective survey of a clinical database (January 2004 to January 2005) of quantitative cell counts from sputum selected from expectorate in patients with obstructive airways diseases was used to identify predictors of bronchiectasis using ROC curves. This was prospectively evaluated (February 2005 to April 2008) using high-resolution computed tomography scans of thorax that were independently scored by a radiologist who was blinded to the clinical details.

RESULTS:

The retrospective survey identified 41 patients with bronchiectasis among 490 patients with airway diseases. Total cell count of 60×106/g or greater of the selected sputum with predominant neutrophils on two occasions had a sensitivity of 86.7%, a specificity of 87.5%, and positive and negative predictive values of 93% and 78%, respectively, to identify bronchiectasis. In the prospective study, 10 of 14 (71%) patients who met these criteria were identified to have bronchiectasis. Both total cell count and the percentage of neutrophils correlated with radiographic bronchiectasis severity.

CONCLUSIONS:

Persistent or recurrent intense sputum cellularity with neutrophilia is suggestive of bronchiectasis.

BACKGROUND:

Sputum cell counts have identified inflammatory subtypes of bronchitis in relatively small numbers of subjects with asthma, chronic obstructive pulmonary disease (COPD) and chronic cough in research studies. The prevalence of different subtypes of bronchitis in routine clinical practice, however, has not been reported.

OBJECTIVE:

To examine the heterogeneity of bronchitis and its relationship to the severity of airflow obstruction.

METHODS:

A retrospective cross-sectional survey based on a computerized database of spontaneous or induced sputum cell counts examined in a large university tertiary respiratory outpatient clinic.

RESULTS:

The database contained 4232 consecutive sputum records from 2443 patients with chronic cough (39%), asthma (37%), asthma with COPD (9%), COPD (13%) and bronchiectasis (3%). Total and differential cell counts were obtained from 86% of successful sputum samples. Induced sputum provided more viable samples than spontaneous expectorate. Approximately one-third of patients with asthma and one-fifth of patients with COPD experience eosinophilic bronchitis. Asthmatic patients with moderate to severe airflow obstruction had a greater number of sputum eosinophils. There was a significantly higher number of total cell counts and percentage of neutrophils in the sputum of COPD patients with moderate and severe airflow obstruction than in those with mild airflow obstruction.

CONCLUSION:

There is heterogeneity in the cellularity of sputum in various airway diseases. Patients with clinically stable airway diseases may have high sputum cell counts. During exacerbations, more patients may experience neutrophilic bronchitis. Severity of airflow obstruction is associated with eosinophilic bronchitis in patients with asthma, and neutrophilic bronchitis in patients with nonasthmatic COPD.

BACKGROUND:

Air pollution caused by motor vehicle emissions has been associated with exacerbations of obstructive airway diseases; however, the nature of the resulting bronchitis has not been quantified.

OBJECTIVE:

To examine whether proximity to major roads or highways is associated with an increase in sputum neutrophils or eosinophils, and to evaluate the effect of proximity to roads on spirometry and exacerbations in patients with asthma.

METHODS:

A retrospective study of 485 sputum cell counts from patients attending a tertiary chest clinic in Hamilton, Ontario, identified eosinophilic or neutrophilic bronchitis. Patients’ residences were geocoded to the street network of Hamilton using geographic information system software. Associations among bronchitis, lung function, and proximity to major roads and highways were examined using multinomial logistic and multivariate linear regression analyses adjusted for patient age, smoking status and corticosteroid medications.

RESULTS:

Patients living within 1000 m of highways showed an increased risk of bronchitis (OR 3.8 [95% CI 1.0 to 13.7]; P<0.05), particularly neutrophilic bronchitis (OR 4.7 [95% CI 1.2 to 18.7]; P<0.05) as well as an increased risk of an asthma diagnosis (OR 1.9 [95% CI 1.0 to 3.4]; P<0.05). Patients living within 300 m of a major road were at increased risk for an asthma exacerbation (OR 1.9 [95% CI 1.5 to 15.5]; P<0.01) and lower lung function, particularly in women (P=0.036).

CONCLUSION:

In patients with airway diseases, living close to a highway or major road was associated with neutrophilic bronchitis, an increased risk of asthma diagnosis, asthma exacerbations and lower lung function.

This case reports the unique association of eosinophilic gastrointestinal disease with eosinophilic bronchitis, asthma and chronic rhinosinusitis and some features of lymphocytic hypereosinophilic syndrome, describes a diagnostic protocol for patients with asthma and persistent eosinophilic bronchitis, and suggests that the use of a novel EPX-mAb provides a reliable method to identify eosinophilic inflammation.

Cell counts in nasal secretions are not used in routine clinical practice to decide on anti-inflammatory or antimicrobial therapy. This study investigated the reproducibility, reliability (validity), and responsiveness of cell counts in blown nasal secretions with a view to implementing this in routine clinical practice. Nasal secretions were obtained from 19 subjects with allergic rhinitis on 3 days in random order (each separated by 1–2 days) by spontaneously blowing their noses (on 2 days) and by a nasal lavage by the modified Grunberg method on the 3rd day. Total and differential cell counts were performed after dispersing the solutions with dithiothreitol as described previously. At the end of the study, subjects had 1 week of open label treatment with nasal corticosteroids if they had nasal eosinophilia or an antibiotic if they had nasal neutrophilia. If the cell counts were normal, they were not treated. The proportion of eosinophil (%) was highly reproducible (intraclass correlation coefficient [ICC], 0.93), and the total cell count (×106/g) and the proportion of neutrophil (%) were modestly reproducible in blown nasal secretions (ICC, 0.46 and 0.55, respectively). The total cell count was consistently and significantly higher in the blown nasal secretions. The proportion of eosinophils (Rs = 0.4; p < 0.05) and neutrophils (Rs = 0.6; p < 0.05) showed modest correlation in the two types of samples. The responsiveness index for eosinophil count was 4.0 and for neutrophil count was 1.5. Total and differential cell counts can be reliably and reproducibly obtained from spontaneously blown nasal secretions. The cell counts are responsive to treatment and can help identify allergic and infective rhinosinusitis and guide therapy and are easy to implement in routine clinical practice.

BACKGROUND:

In a four-centre trial, the use of sputum cell counts (sputum strategy [SS]) to guide treatment had resulted in fewer and less severe exacerbations without the need for a higher corticosteroid dose, compared with the use of symptoms and spirometry (clinical strategy [CS]).

OBJECTIVE:

To compare the cost of the SS with the CS in the treatment of patients with moderate to severe asthma.

METHODS:

In 39 patients (19 in the SS, 20 in the CS) from one of the centres, the cost (third-party payer) of the two treatment strategies was compared. Resource use data were collected using a structured questionnaire. Corresponding unit costs in 2006 Canadian dollars were obtained.

RESULTS:

The clinical characteristics of the patients were similar to the study population at the four centres. In the SS, the number of visits to a family physician for health disorders indirectly related to asthma (P=0.003) and the amount of inhaled long-acting beta-agonists (P=0.007) were less than that of the CS. While the total estimated median cost per patient for spirometry ($393; range $299 to $487) was less than that for sputum induction ($1,008; range $907 to $1,411), the total cost of the SS ($2,265; range $1,466 to $4,347) was less than that of the CS ($3369; range $2208 to $3927) (P=0.216). This cost difference was due to lower costs of physician and hospital visits and services (P=0.078), of inhaled short-acting bronchodilators (P=0.067), of long-acting beta-agonists (P=0.002) and of inhaled corticosteroids (P=0.064) in the SS.

CONCLUSION:

In patients with moderate to severe asthma, the use of sputum cell counts to guide treatment is more effective and is likely to be less costly than management using symptoms and spirometry.