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1.  Quantitative sputum cell counts to monitor bronchitis: A qualitative study of physician and patient perspectives 
Many common diseases affecting the airways are characterized by airway inflammation. The measurement of this inflammation has a significant role in the management of these diseases. Quantitative sputum cell counts provide a measurement of the type and severity of inflammation present. Sputum cell counts are used in routine clinical practice in some centres but their use is not widespread. The present study used a standardized questionnaire to determine both patients’ and physicians’ attitudes toward the use of sputum cell counts. The use of sputum cell counts was well accepted by patients and physicians. Ninety per cent of patients were satisfied with the test. Sixty per cent of family physicians were satisfied with the test and 80% were in favour of it being funded by the government. The authors recommend more widespread use of sputum cell counts to guide the management of airway diseases.
PMCID: PMC3628647  PMID: 23457675
Asthma; Bronchitis; Patient satisfaction; Sputum cell counts; Willingness to pay
2.  Local and systemic immunological parameters associated with remission of asthma symptoms in children 
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.
PMCID: PMC3599667  PMID: 23043798
Asthma in children; Eosinophils; IL-5; TNF-α; IL-12
3.  Persistent sputum cellularity and neutrophils may predict bronchiectasis 
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.
Quantitative cell counts in sputum provide an accurate assessment of the type and severity of bronchitis.
To examine whether sputum cell counts could identify bronchiectasis in patients with recurrent bronchitis.
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.
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.
Persistent or recurrent intense sputum cellularity with neutrophilia is suggestive of bronchiectasis.
PMCID: PMC3205103  PMID: 22059180
Bronchiectasis; Neutrophil; Sputum cell counts
5.  Heterogeneity of bronchitis in airway diseases in tertiary care clinical practice 
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.
To examine the heterogeneity of bronchitis and its relationship to the severity of airflow obstruction.
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.
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.
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.
PMCID: PMC3328881  PMID: 21766077
Asthma; Bronchitis heterogeneity; Clinical practice; COPD; Sputum cell counts
8.  Association between proximity to major roads and sputum cell counts 
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.
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.
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.
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).
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.
PMCID: PMC3071007  PMID: 21369545
Asthma; Bronchitis; Exacerbations; Geospatial analysis; Road traffic; Sputum cell counts
10.  Reproducibility, validity, and responsiveness of cell counts in blown nasal secretions 
Allergy & Rhinology  2011;2(1):3-5.
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.
PMCID: PMC3390126  PMID: 22852107
Blown nasal secretions; cell counts; nasal lavage; repeatability; validity
11.  Cost analysis of monitoring asthma treatment using sputum cell counts 
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]).
To compare the cost of the SS with the CS in the treatment of patients with moderate to severe asthma.
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.
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.
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.
PMCID: PMC2679573  PMID: 18949107
Asthma; Cost; Spirometry; Sputum cell counts; Symptoms
12.  Playing cards on asthma management: A new interactive method for knowledge transfer to primary care physicians 
To describe an interactive playing card workshop in the communication of asthma guidelines recommendations, and to assess the initial evaluation of this educational tool by family physicians.
Family physicians were invited to participate in the workshop by advertisements or personal contacts. Each physician completed a standardized questionnaire on his or her perception of the rules, content and properties of the card game.
A university-based continuing medical education initiative.
Primary care physicians.
Physicians’ evaluation of the rules, content and usefulness of the program.
The game allowed the communication of relevant asthma-related content, as well as experimentation with a different learning format. It also stimulated interaction in a climate of friendly competition. Participating physicians considered the method to be an innovative tool that facilitated reflection, interaction and learning. It generated relevant discussions on how to apply guideline recommendations to current asthma care.
This new, interactive, educational intervention, integrating play and scientific components, was well received by participants. This method may be of value to help integrate current guidelines into current practice, thus facilitating knowledge transfer to caregivers.
PMCID: PMC2677773  PMID: 18060093
Asthma; Game-based learning; Knowledge implementation; Medical education
13.  Sputum neutrophilia can mask eosinophilic bronchitis during exacerbations 
Exacerbations of airway disease are eosinophilic, neutrophilic, both or neither. The primary objective of the present study was to identify whether the treatment of a neutrophilic bronchitis can unmask an associated eosinophilia.
A retrospective survey of 2160 consecutive sputum cell counts from 1343 patients with airway disease was conducted to identify patients with an isolated neutrophilic bronchitis, which was defined as a sputum total cell count of greater than or equal to 12×106 cells/g of sputum and a proportion of neutrophils of 80% or greater. The characteristics of the patients who subsequently demonstrated sputum eosinophilia (3% or greater) within eight weeks of resolving the neutrophilia were compared with the patients who subsequently did not have sputum eosinophilia.
Two hundred thirty-seven patients had 273 neutrophilic exacerbations. The sputum was re-examined within eight weeks in 65 patients (27.4%), of whom 38 (58.5%) had resolution of the neutrophilic bronchitis after treatment with an antibiotic. Of these 38 patients, 13 (34%) showed eosinophilia.
A neutrophilic exacerbation of airway disease was observed to mask sputum eosinophilia in one-third of patients who had sputum cell counts available before and after antibiotic therapy. Hence, the absence of sputum eosinophilia during an infective exacerbation should not be used as an indication to reduce the dose of corticosteroids. To optimize therapy, repeat sputum cell count measurements are recommended after antibiotic treatment before changing corticosteroid treatment.
PMCID: PMC2676394  PMID: 17703243
Eosinophilic bronchitis; Neutrophilic bronchitis; Sputum cell counts
14.  The efficiency of sputum cell counts in cystic fibrosis 
Technical factors relating to processing viscid sputum in cystic fibrosis (CF) and their influence on the reproducibility and validity of cell counts need to be evaluated. In addition, the methods need to be standardized so that they can be applied clinically and in research.
To examine the efficiency, reliability and validity of processing small volumes of spontaneously expectorated sputum from subjects with CF.
Sputum was collected from adults with CF (n=35) and compared with sputum from adults with infective bronchitis or bronchiectasis (IB/B) (n=16), or with asthma or chronic obstructive pulmonary disease (AS/COPD) (n=25). Selected sputum (100 mg to 200 mg) was processed with dithiothreitol (0.1%) and filtered. Total cell count (TCC) and viability were obtained in a counting chamber and cytospins were prepared and stained with Wright’s for a differential cell count. Sputum and filter remnant were processed for TCC, viability and differential cell count, and the efficiency was determined by comparing the mean loss in cell yield to the filter. Two different portions from the same sputum sample were processed for cell counts to determine reproducibility. Results were compared with those from IB/B and AS/COPD groups.
Efficiency of cell dispersal was excellent and similar to that in AS/COPD and IB/B groups. Reproducibility of cell counts from two portions of a sputum sample was high (R≥0.80). CF sputum demonstrated a raised TCC and neutrophilia similar to IB/B but significantly higher than AS/COPD.
The selection method of evaluating cell counts in viscid CF sputum is efficient, reproducible and valid.
PMCID: PMC2676380  PMID: 17372637
Airway inflammation; Cystic fibrosis; Sputum cell counts
15.  Predictors of loss of asthma control induced by corticosteroid withdrawal 
Asthma guidelines recommend reducing the dose of inhaled corticosteroids after establishing control.
To identify predictors of loss of control and the kinetics of symptoms, and inflammatory and physiological measurements when inhaled corticosteroids are reduced in patients with stable asthma.
In a single-blind study, the daily dose of inhaled corticosteroid was reduced by one-half at intervals of 20±2 days in 17 adults with controlled asthma until loss of asthma control occurred or until the corticosteroid was replaced with placebo for 20 days. The patients recorded symptoms and peak expiratory flow each day, and forced expiratory volume in 1 s (FEV1), the provocative concentration of methacholine causing a 20% fall in FEV1 (PC20), exhaled nitric oxide, and eosinophils in sputum and blood were measured every 10 days. A loss of asthma control was defined as a worsening of the symptoms score of at least 20%, and either a decrease in FEV1 of at least 15% or a decrease in PC20 of at least fourfold.
Two patients had a respiratory infection and were withdrawn from the study. In eight patients, asthma became uncontrolled after a mean of 33 days (range 13 to 48 days). This was accurately reflected by a worsening of all parameters. The first parameter to change was the sputum eosinophil percentage (20 days before the loss of asthma control). Significant changes in exhaled nitric oxide, FEV1 and methacholine PC20 were observed only when the symptoms became uncontrolled. A high blood eosinophil count at baseline (risk ratio of 2.5, 95% CI 1.0 to 6.5) and an increase in sputum eosinophil count after the reduction of corticosteroids were predictors of loss of asthma control.
In patients whose asthma is controlled on inhaled corticosteroid, it is prudent not to reduce the dose further if the blood eosinophils are increased or if the sputum eosinophils increase by as little as 1% after the reduction of corticosteroids.
PMCID: PMC2539017  PMID: 16642226
Asthma exacerbation; Eosinophils; Induced sputum; Inhaled corticosteroid
16.  Smoking, season, and detection of chlamydia pneumoniae DNA in clinically stable COPD patients 
The prevalence and role of Chlamydia pneumoniae in chronic obstructive pulmonary disease (COPD) remain unclear.
Peripheral blood mononuclear cells were obtained from 100 outpatients with smoking-related, clinically stable COPD, and induced sputum was obtained in 62 patients.
Patients had mean age (standard deviation) of 65.8 (10.7) years, mean forced expiratory volume in one second of 1.34 (0.61) L, and 61 (61.0%) were male. C. pneumoniae nucleic acids were detected by nested polymerase chain reaction in 27 (27.0%). Current smoking (odds ratio {OR} = 2.6, 95% confidence interval {CI}: 1.1, 6.6, P = 0.04), season (November to April) (OR = 3.6, 95% CI: 1.4, 9.2, P = 0.007), and chronic sputum production (OR = 6.4, 95% CI: 1.8, 23.2, P = 0.005) were associated with detection of C. pneumoniae DNA.
Prospective studies are needed to examine the role of C. pneumoniae nucleic acid detection in COPD disease symptoms and progression.
PMCID: PMC117240  PMID: 12098361
18.  Investigation and Management of Rhinitis 
Canadian Family Physician  1979;25:1221-1224.
The family physician is ideally situated to deal with most chronic-recurrent nasal problems. The physician is alerted to the real problem by the recognition that terms such as 'sinus' and 'colds' often camouflage the problem of chronic rhinitis and chronic nasal obstruction. Avoidance of offending substances, the use of medications, the occasional judicious use of allergen injection treatment and sometimes surgical intervention for nasal polyps provide different modalities of treatment which can have a major beneficial effect upon symptoms. Improved results are often achieved with a more analytic approach to the use of antihistimine and the availability of topical steroids and topical cromoglycate. The treatment method described embodies a systematic approach involving the sequential addition of modalities until specified objectives are achieved.
PMCID: PMC2383238  PMID: 21297799
19.  II. The late asthmatic responses 
Immediate asthmatic responses have been regarded as the characteristic type of asthmatic response to follow exposure to inhaled allergens in patients with extrinsic asthma. They begin within minutes, clear within one to three hours and are inhibited by disodium cromoglycate but not by corticosteroids. They involve the reaction of antigen with antibodies usually of the IgE class. In recent years allergen inhalation tests have demonstrated the frequent occurrence of late asthmatic responses, either following immediate responses (dual responses) or occurring in isolation. The late asthmatic responses begin two to six hours after the allergen challenge, are prolonged and often severe, and are inhibited by both disodium cromoglycate and corticosteroids. The mechanisms involved in their provocation are not clearly understood but from the allergic viewpoint they may involve the participation of IgG ± IgM antibodies and/or IgE antibodies. Late asthmatic responses explain the frequent occurrence of allergen-induced prolonged asthma. Their features suggest that they are more important than immediate responses in the pathophysiology of asthma.
PMCID: PMC1947300  PMID: 4130351

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