Incidence of cardiovascular disease in a cohort of mine workers exposed to ultrafine aluminum powder in Ontario, Canada.

BACKGROUND: A retrospective cohort study was conducted to estimate associations between an ultrafine aluminum powder, McIntyre Powder (MP), and cardiovascular disease incidence in a cohort of mine workers from Ontario, Canada. Disease outcomes included ischemic heart disease (IHD), acute myocardial infarction (AMI), congestive heart failure (CHF), and strokes and transient ischemic attacks (STIA). METHODS: Using work history records from the Ontario Mining Master File (MMF) mine workers were followed for disease incidence in administrative health records. The analysis included 25,813 mine workers who were exposed to MP between 1943 and 1979 and followed for cardiovascular disease (CVD) diagnoses between 2006 and 2018. Cardiovascular disease cases were ascertained using physician, hospital, and ambulatory care records. Poisson regression models were used to estimate age and birth-year adjusted incidence rate ratios (RR) and 95% confidence intervals (CI) for associations between MP exposure and CVD outcomes. RESULTS: Ever-exposure to MP was positively associated with modest increases in the incidence rate of IHD, AMI, and CHF, but not STIA, using both assessment approaches. Duration of self-reported MP exposure was positively associated with monotonically increasing rates of IHD and AMI compared to never-exposed miners, with the greatest association observed among miners with >20 years of exposure (for IHD: RR 1.24, 95% CI: 0.91-1.68; and for AMI: RR 1.52, 95% CI 1.01-2.28). CONCLUSION: Mine workers ever-exposed to MP had modestly elevated rates of CVD. The rate of CVD diagnoses appeared to increase with longer duration of exposure when assessed by both self-reported exposure and through historical records.

Participatory Development Process of Two Human Dimension Intervention Programs to Foster Physical Fitness and Psychological Health and Well-Being in Wildland Firefighting.

Intervention programs designed, delivered, and evaluated by and within organizations are a critical component in the promotion of employee health and well-being and in the prevention of occupational injury. Critical for transference of findings across complex occupational settings is a clearly articulated development process, a reliance on and evaluation of underlying theoretical foundations, and the inclusion of relevant outcomes emerging out of participatory action processes. To date, there have been no documented efforts outlining the development, implementation, or evaluation of human dimension intervention programs targeting wildland firefighters. The purpose of this paper is to outline the development of two collaborative and participatory intervention programs, targeting wildland firefighters' physical and psychological health and well-being. Two human dimension intervention programs were developed in a collaborative, iterative and participatory process following the Context-Content-Process-Outcomes Framework. First, a physical fitness training intervention program was designed to maintain wildland firefighter's physical fitness levels and attenuate risk of injury. Second, a psychosocial education intervention program was developed to mitigate the impact of psychosocial risk factors, foster work engagement, and decrease job stress. The current study provides evidence for the capacity of researchers and organizations to collaboratively develop practical programs primed for implementation and delivery.

High-intensity interval exercise in the cold regulates acute and postprandial metabolism.

High-intensity interval exercise (HIIE) has been shown to be more effective than moderate-intensity exercise for increasing acute lipid oxidation and lowering blood lipids during exercise and postprandially. Exercise in cold environments is also known to enhance lipid oxidation; however, the immediate and long-term effects of HIIE exercise in cold are unknown. The purpose of this study was to examine the effects cold stress during HIIE on acute exercise metabolism and postprandial metabolism. Eleven recreationally active individuals (age: 23 ± 3 yr, weight: 80 ± 9.7 kg, V̇O2peak: 39.2 ± 5.73 mL·kg-1·min-1) performed evening HIIE sessions (10 × 60 s cycling, 90% V̇O2peak interspersed with 90 s active recovery, 30% V̇O2peak) in thermoneutral (HIIE-TN, control; 21°C) and cold environment (HIIE-CO; 0°C), following a balanced crossover design. The following morning, participants consumed a high-fat meal. Indirect calorimetry was used to assess substrate oxidation, and venous blood samples were obtained to assess changes in noncellular metabolites. During acute exercise, lipid oxidation was higher in HIIE-CO (P = 0.002) without differences in V̇O2 and energy expenditure (P ≥ 0.162) between conditions. Postprandial V̇O2, lipid and CHO oxidation, plasma insulin, and triglyceride concentrations were not different between conditions (P > 0.05). Postprandial blood LDL-C levels were higher in HIIE-CO 2 h after the meal (P = 0.003). Postprandial glucose area under curve was 49% higher in HIIE-CO versus HIIE-TN (P = 0.034). Under matched energy expenditure conditions, HIIE demonstrated higher lipid oxidation rates during exercise in the cold; but only marginally influenced postprandial lipid metabolism the following morning. In conclusion, HIIE in the cold seemed to be less favorable for postprandial lipid and glycemic responses.NEW & NOTEWORTHY This is the first known study to investigate the effects of cold ambient temperatures on acute metabolism during high-intensity interval exercise, as well as postprandial metabolism the next day. We observed that high-intensity interval exercise in a cold environment does change acute metabolism compared to a thermoneutral environment; however, the addition of a cold stimulus was less favorable for postprandial metabolic responses the following day.

Safety Culture: A Retrospective Analysis of Occupational Health and Safety Mining Reports.

BACKGROUND: In the mining industry, various methods of accident analysis have utilized official accident investigations to try and establish broader causation mechanisms. An emerging area of interest is identifying the extent to which cultural influences, such as safety culture, are acting as drivers in the reoccurrence of accidents. Thus, the overall objective of this study was to analyze occupational health and safety (OHS) reports in mining to investigate if/how safety culture has historically been framed in the mining industry, as it relates to accident causation. METHODS: Using a computer-assisted qualitative data analysis software, 34 definitions of safety culture were analyzed to highlight key terms. Based on word count and contextual relevance, 26 key terms were captured. Ten OHS reports were then analyzed via an inductive thematic analysis, using the key terms. This analysis provided a concept map representing the 50-year data set and facilitated the use of text framing to highlight safety culture in the selected OHS mining reports. RESULTS: Overall, 954 references and six themes, safety culture, attitude, competence, belief, patterns, and norms, were identified in the data set. Of the 26 key terms originally identified, 24 of them were captured within the text. The results made evident two distinct frames in which to interpret the data: the role of the individual and the role of the organization, in safety culture. CONCLUSION: Unless efforts are made to understand and alter cultural drivers and share these findings within and across industries, the same accidents are likely to continue to occur.

Ambient temperature influences metabolic substrate oxidation curves during running and cycling in healthy men.

Fat oxidation in cold environments and carbohydrate (CHO) use in hot environments are increased during exercise at steady-state submaximal workloads. However, the influence of cold and heat on fat and CHO oxidation curves remain unknown. We therefore examined the influence of a cold and warm ambient temperature on fat and CHO oxidation across a wide range of exercise intensities during treadmill and cycle ergometer exercise. Nine, young, healthy, male subjects completed four trials, during which they performed an incremental peak oxygen consumption (⩒O2peak) test on a cycle ergometer or treadmill in a 4.6°C or 34.1°C environment. Substrate oxidation, maximal fat oxidation rate (MFO), and exercise intensity where MFO occurs (Fatmax) were assessed via indirect calorimetry. MFO was significantly greater in the cold vs. warm during the treadmill exercise (0.66 ± 0.31 vs. 0.43 ± 0.23 g min-1; p = 0.02) but not during cycling (0.45 ± 0.24 vs. 0.29 ± 0.11 g min-1; p = 0.076). MFO was also greater during treadmill vs. cycling exercise, irrespective of ambient temperature (0.57 g min-1 vs. 0.37 g min-1; p = 0.04). Fatmax was greater in the cold vs. warm for both treadmill (57 ± 20 vs. 37 ± 17%⩒O2peak; p = 0.025) and cycling (62 ± 28 vs. 36 ± 13%⩒O2peak; p = 0.003). Multiple, linear, mixed-effects regressions revealed a strong influence of ambient temperature on substrate oxidation. We demonstrated that exercising in a cold environment increases MFO and Fatmax, predominantly during treadmill exercise. These results validate the implication of ambient temperature on energy metabolism over a wide range of exercise intensities.

An Assessment of the Validity of an Audio-Video Method of Food Journaling for Dietary Quantity and Quality.

OBJECTIVE: To validate an audio-video (AV) method of food journaling, in a free-living scenario, compared to direct, weighed food assessment. DESIGN AND SETTING: Data were collected in a cafeteria. Meals, selected by participants (n=30), were documented using the AV method: participants video-recorded their tray while audio-recording a description of their selected meal, after which the research team digitally weighed each food item and created an itemized diary record of the food. VARIABLES MEASURED: Data from the AV method and from the weighed food diaries were transcribed and entered into a nutrition software analysis program (Nutribase Pro 10.0). Nutrient outputs were compared between the two methods including kilocalories, macronutrients, and selected micronutrients. ANALYSES: Using mean scores for each variable, Wilcoxon signed-rank test and Spearman's correlation coefficients were conducted. Interclass correlation coefficient (ICC) was calculated for absolute agreement between the two methods to assess interrater reliability. RESULTS: With the exception of Vitamin E and total weight, nutrient values were highly correlated between methods and were statistically significant given alpha = 0.05, power = 0.95, and effect size of 0.70. CONCLUSIONS: The AV method may be a meaningful alternative to diary recording in a free-living setting.

Effect of a Simulated Mine Rescue on Physiological Variables and Heat Strain of Mine Rescue Workers.

OBJECTIVE: To describe physiological responses of mine rescuers during a simulated mine emergency. METHODS: Body-worn monitors (n = 74) and core temperature (Tc) capsules (n = 54) assessed heart rate (HR), respiration rate (RR), energy expenditure (EE), oxygen consumption ((Equation is included in full-text article.)), Tc and skin temperature (Tskin), by team position and task. A multivariate analysis was performed with team positions, tasks, and measures as factors. RESULTS: HRmean and HRpeak were 78.6% and 94.5%, respectively, of predicted maximum heart rate. Arduous labor tasks elicited higher HR, RR, and (Equation is included in full-text article.)than casualty care. Captains exhibited lower HRmean, HRpeak, RR, RRpeak, (Equation is included in full-text article.), Tc, and Tskin compared with other positions. Tc mean exceeded 38.6 °C (n = 14 recorded Tc >39 °C). CONCLUSIONS: Captains' physical loading and heat stress were lowest. Nonetheless, all tasks and positions induced high physical load and heat strain.

Sleep Quantity and Quality of Ontario Wildland Firefighters Across a Low-Hazard Fire Season.

OBJECTIVE: The aim of the study was to assess the sleep quality, quantity, and fatigue levels of Canadian wildland firefighters while on deployment. METHODS: Objective and subjective sleep and fatigue measures were collected using actigraphy and questionnaires during non-fire (Base) and fire (Initial Attack and Project) deployments. RESULTS: Suboptimal sleep quality and quantity were more frequently observed during high-intensity, Initial Attack fire deployments. Suboptimal sleep was also exhibited during non-fire (Base) work periods, which increases the risk of prefire deployment sleep debt. Self-reported, morning fatigue scores were low-to-moderate and highest for Initial Attack fire deployments. CONCLUSIONS: The study highlights the incidence of suboptimal sleep patterns in wildland firefighters during non-fire and fire suppression work periods. These results have implications for the health and safety practices of firefighters given the link between sleep and fatigue, in a characteristically hazardous occupation.

Anti-allergic therapies: effects on eosinophil progenitors.

Marked eosinophilic infiltration is the typical inflammatory response associated with allergic inflammation. Previous research involving animal and human models has established a role for the eosinophil/basophil hematopoietic progenitor in a systemic process of allergic inflammation. In this article, we will review the evidence implicating eosinophil/basophil progenitors in this systemic response and will discuss the rationale for targeting this cell in the treatment of allergic disease. In this context, we discuss corticosteroid treatment of allergic diseases, such as asthma and its effects on hematopoietic mechanisms, the effects of therapies that inhibit the actions of cysteinyl leukotrienes, the effects of in vivo blockade of the eosinophil-active cytokine interleukin-5, and the effects of antihistamines on hematopoiesis. It is suggested that several anti-allergic therapies exert their beneficial effects on allergic inflammation by influencing eosinophil production systemically. Therefore, targeting the systemic hematopoietic response may provide additional, more beneficial, therapeutic effects.

Increased levels of airway neutrophils reduce the inhibitory effects of inhaled glucocorticosteroids on allergen-induced airway eosinophils.

BACKGROUND: Treatment with inhaled glucocorticosteroids attenuates allergen-induced airway inflammation but is less effective in people with asthma who have noneosinophilic airway inflammation. OBJECTIVE: Studies in which glucocorticosteroid treatment was used before allergen challenges were re-examined to determine whether the efficacy of steroid treatment could be predicted by baseline levels of sputum inflammatory cells. PATIENTS AND METHODS: Twenty-eight nonsmoking subjects with atopic asthma controlled by beta2-agonists participated in only one of three studies, each carried out with a double-blind, placebo controlled, randomized, crossover design. Subjects were treated with glucocorticosteroids or placebo for six to eight days and then underwent allergen inhalation challenge. Spirometry was measured for 7 h after allergen challenge, and then sputum inflammatory cells were measured. Sputum inflammatory cells were also measured before and after treatment, and 24 h after allergen challenge. The per cent inhibition of the allergen-induced airway responses by glucocorticosteroids was calculated. RESULTS: Inhaled glucocorticosteroids significantly attenuated the early and late asthmatic responses, and the number of allergen-induced sputum eosinophils (P<0.05). There was a significant negative relationship between the number of sputum neutrophils at baseline, and the per cent inhibition of allergen-induced sputum eosinophils measured at 7 h (r=-0.61, P<0.001) and 24 h (r=-0.73, P<0.0001) after challenge, suggesting that glucocorticosteroids are less effective in attenuating allergen-induced airway inflammation in subjects with high levels of neutrophils. There was no correlation between the number of sputum eosinophils at baseline and the per cent inhibition of allergen-induced responses. CONCLUSIONS: Baseline airway neutrophils, not eosinophils, can be used to predict the efficacy of inhaled steroids on allergen-induced sputum eosinophils.

Recommendations for Tobacco Control on Post-Secondary Campuses that are Geographically Isolated.

BACKGROUND: Many Ontarians continue to report exposure to second-hand smoke in public spaces. Completely smoke-free environments are the preferred and socially responsible option for non-smoking policies; however, when considering the variety of landscapes in which post-secondary institutions are located, 'a one size fits all' smoking policy is unrealistic to implement and enforce. The purpose of the study was to: 1) gain a better sense of the prevalence of smoking and exposure to second-hand smoke in a post-secondary context that is geographically isolated; 2) assess the awareness of existing non-smoking initiatives; and 3) identify preferred approaches for tobacco control. METHODS: An online survey was distributed in 2012 to all members of the Laurentian University community. Descriptive statistics are presented, using frequency distributions, and group comparisons are reported, using Chi-Square analyses. RESULTS: A total of 1282 persons completed the survey. Nearly 80% of respondents reported that they had been exposed to second-hand smoke in the past month on campus and the majority of respondents felt that smoking should only be allowed in Designated Outdoor Smoking Areas (51.5%); including 37.3% of daily smokers and occasional smokers. CONCLUSION: Institutions with a geographically isolated campus, which limit options to divert smokers from public entrances, should consider the use of Designated Outdoor Smoking Areas. Implementation will create immediate reductions in the prevalence of smoking at building entrances and in high traffic locations and will therefore protect non-smokers from the dangers of environmental tobacco smoke.

Evaluating the reliability of assessing home-packed food items using digital photographs and dietary log sheets.

OBJECTIVE: To assess the reliability of manual data entry for home-packed food items by using digital photographs and dietary log sheets. METHODS: Data from 60 lunches were entered by researcher A and B independently. Researcher B re-entered researcher A's items within 1 week. Researcher B then re-entered her items 4 weeks from the initial entry point. RESULTS: The inter-rater reliability intraclass correlation coefficient (ICC) was 0.83 for total kilocalories and ranged from 0.75-0.87 for macronutrients. The intra-rater reliability ICC was 0.92 for total kcal and ranged from 0.90-0.92 for macronutrients. The inter-rater ICCs for the 5 selected micronutrients ranged from 0.33-0.83, whereas the intra-rater ICCs for these micronutrients ranged from 0.65-0.98. CONCLUSIONS AND IMPLICATIONS: This method of data entry is feasible and its reliability is promising for macronutrient investigations. Continued assessment of this method for investigations related to micronutrient content is recommended.

Examining school-based pedometer step counts among children in grades 3 to 6 using different timetables.

BACKGROUND: Advocates for the implementation of the Balanced School Day (BSD) schedule argue that this schedule will increase opportunities for physical activity. However, the relationship between this scheduling change and its impact on physical activity has not been examined. Thus, this study assessed levels of physical activity in students attending 2 different schools: 1 using the BSD and the other using the Traditional School Day (TSD) schedule. METHODS: Participation of students between grades 3 and 6 was sought. Data were collected over 4 school days using pedometers. Independent Sample t tests and 1-way analysis of variance (ANOVA) were performed. RESUTLS: A total of 117 students participated. Overall, average daily step counts for boys (6972 ± 1952) were significantly higher than girls (5742 ± 1495; p < .001). These average step counts represent 47% and 48% of the recommended amount of steps needed for health benefits for children between the ages of 6 and 12. The average daily step count for students using the BSD schedule was 6017 (±1666), while the average daily step count for students using the TSD schedule was 6788 (±1987). The difference in steps (771) was statistically significant (p = .03). CONCLUSIONS: These results do not support claims that the BSD offers increased physical activity. In fact, these results suggest that students enrolled in schools using the BSD schedule may have reduced daily physical activity. In addition, these results demonstrate that overall school-based physical activity is less than half of the recommended level; independent of school scheduling.

Alcohol fixation of induced sputum samples for applications in rural communities.

BACKGROUND: Sputum induction is a tool recommended for the assessment of airway inflammation and disease management. Currently, its use is limited because samples need to be processed within 3 h of induction (ie, while cells are viable); therefore, this procedure is unavailable to most clinicians. OBJECTIVE: To develop a fixation method for induced sputum samples that allows for a delay in processing while maintaining sample integrity and not altering the standard processing method. METHODS: Sputum samples were collected and split into three portions: a fresh sample processed using the routine method (within 3 h, using dithiothreitol); fixation in alcohol followed by delayed processing using the routine method (within 48 h to 72 h, using dithiothreitol); and fixation in formaldehyde followed by delayed processing using an alternative method (within 48 h to 72 h, using proteolysis). For each method, cytospins were prepared and differential cell counts were performed. RESULTS: Fixation in alcohol provides accurate measures of eosinophils and macrophages, but not neutrophils. Formaldehyde fixation provides accurate measures of neutrophils and macrophages, but not eosinophils. DISCUSSION: Alcohol fixation is a superior method for eosinophil quantification. It requires alteration of standardized methods for sputum sample processing and should be recommended for monitoring eosinophilic airway disease in settings where immediate processing of a sputum sample is not possible.

In vitro effects of budesonide on eosinophil-basophil lineage commitment.

UNLABELLED: IL-5 is the primary cytokine that stimulates the production and survival of eosinophils and basophils from progenitor cells. The inhaled glucocorticoid, budesonide, has been shown to exert a therapeutic effect via suppression of eosinophil/basophil progenitors in vivo. Since various steroids have exhibited the ability to enhance eosinophil/basophil progenitor differentiation, we examined the effects of budesonide in vitro. Bone marrow and cord blood samples were obtained and cultured in the presence of IL-5 alone or IL-5 plus budesonide. Eosinophil/basophil colony-forming units were enumerated from cultured nonadherent mononuclear cells and from purified CD34⁺ cells. CD34⁺ cells with and without budesonide were also examined for up-regulation of ERK1/2, MAPK and GATA-1 using real time-PCR. RESULTS: i) up-regulation of eosinophil/basophil colony-forming units is due to the direct effects of budesonide on IL-5-stimulated progenitors; ii) GATA-1 is likely involved in the early amplification of eosinophil/basophil progenitor commitment leading to increased differentiation. A potential transcriptional pathway has been identified which may mediate the effects of budesonide on eosinophil/basophil lineage commitment.

Protection by budesonide and fluticasone on allergen-induced airway responses after discontinuation of therapy.

BACKGROUND: Treatment with inhaled steroids is an effective method of reducing bronchoconstriction and airway inflammation after allergen challenge. However, the duration of the protective effects of inhaled steroids after discontinuation of therapy has not been established. OBJECTIVE: We sought to evaluate the protective effect of 1 week of inhaled steroid therapy against inhaled allergen challenge 12 hours after discontinuation of therapy. METHODS: In this randomized, double-blind, placebo-controlled crossover trial, 26 asthmatic subjects (>18 years old) not using inhaled steroids were administered 200 microg of budesonide twice daily, 200 microg of fluticasone twice daily, or placebo twice daily for 1 week. Twelve hours after discontinuation of therapy, subjects were administered an inhaled allergen challenge. Each treatment period was separated by a 3-week washout period. RESULTS: When compared with placebo (26% +/- 14%), there was a slight but significant protection against the allergen-induced early response after fluticasone treatment (19% +/- 10%, P = .001) but not after budesonide treatment (23% +/- 13%, P = .08). However, when the area under the curve for the early airway response was examined, there was no difference between the 2 drugs in the amount of protection ( P = .62). Partial protection was demonstrated against the late-response allergen-induced sputum eosinophilia with both treatments ( P = .001). By contrast, no protection was observed against allergen-induced airway hyperresponsiveness for either treatment. CONCLUSIONS: The protective effects of inhaled steroids against allergen-induced early responses, airway eosinophilia, and allergen-induced airway hyperresponsiveness are partially or completely lost as early as 12 hours after discontinuation of therapy.

Progenitor egress from the bone marrow after allergen challenge: role of stromal cell-derived factor 1alpha and eotaxin.

BACKGROUND: CCR3 expression on CD34+ cells mediates migration to eotaxin in vitro. CXCR4 and stromal cell-derived factor (SDF)-1alpha are important for stem cell homing to hemopoietic compartments. OBJECTIVE: To study chemokine-mediated progenitor cell traffic in allergic inflammation. METHODS: Bone marrow (BM) aspirates were obtained at baseline from normal subjects; atopic subjects without asthma; and subjects with asthma before, 5 hours after, and 24 hours after allergen inhalation (dual and early responders). Changes in chemokine receptor expression and migration were assessed. RESULTS: Expression of CXCR4, but not CCR3, on BM CD34+ cells was greater in normal subjects compared with atopic subjects with asthma. Likewise, SDF-1alpha, but not eotaxin, stimulated a greater migrational response by BM CD34+ cells from normal subjects compared with subjects with asthma. For all subjects, a positive correlation was found between intensity of CXCR4 expression and magnitude of CD34+ cell response to SDF-1alpha. Allergen inhalation attenuated both intensity of CXCR4 expression and SDF-1alpha levels in marrow from dual compared with early responders 24 hours postallergen. In contrast, the intensity of CCR3 expression on BM CD34+ cells increased in dual compared with early responders at 24 hours postallergen. In addition, an increase in migrational responsiveness of BM CD34+ cells to eotaxin and a decrease to SDF-1alpha 24 hours postallergen was found in dual responder subjects with asthma. CONCLUSION: After allergen inhalation in subjects with asthma, a downregulation in CXCR4 intensity on BM CD34+ cells and a reduction in BM SDF-1alpha levels may reduce progenitor retention to marrow stroma promoting peripheral egress, possibly mediated by the CCR3/eotaxin axis.

The effect of cysteinyl leukotrienes on growth of eosinophil progenitors from peripheral blood and bone marrow of atopic subjects.

BACKGROUND: The accumulation of eosinophils into the peripheral blood and airways of asthmatic subjects is, in part, dependent on cysteinyl leukotrienes (cysLTs). However, the effect of cysLTs on peripheral blood and bone marrow eosinophil pro-genitor cells in allergic subjects is not known. OBJECTIVE: The purpose of this study was to evaluate the effects of leukotriene (LT) D(4) and LTE(4) and the cysLT(1) receptor antagonist montelukast on peripheral blood and bone marrow eosinophil-basophil progenitor growth and development in atopic subjects. METHODS: Semisolid methylcellulose cultures for peripheral blood and bone marrow eosinophil-basophil colonies were counted after incubation with or without addition of LTD(4), LTE(4), and montelukast in the presence of suboptimal concentrations of GM-CSF, IL-3, and IL-5. RESULTS: Peripheral blood eosinophil-basophil colony-forming unit cultures grown in the presence of GM-CSF and bone marrow eosinophil-basophil colony-forming units grown in the presence of IL-5 were significantly increased by the addition of LTD(4) (0.1 micromol/L). This increase was suppressed by montelukast (1 micromol/L). CONCLUSION: This study has demonstrated that the cysLT LTD(4) can stimulate proliferation of eosinophil hematopoietic progenitor cells in the presence of eosinophilopoietic cytokines. The suppressive effect by montelukast demonstrates that this is a cysLT(1) receptor-mediated effect.

Sputum CD34+IL-5Ralpha+ cells increase after allergen: evidence for in situ eosinophilopoiesis.

Eosinophil lineage-committed progenitors increase in the bone marrow of subjects with asthma developing allergen-induced airway hyperresponsiveness and eosinophilia. Also, higher numbers of circulating eosinophil/basophil cfu have been demonstrated 24 hours after allergen inhalation and in bronchial and nasal biopsies of allergic individuals. These cells may undergo in situ eosinophilopoiesis, suggesting that after allergen inhalation, progenitor cells traffic from the bone marrow to the airways, providing an ongoing source of effector cells. To examine this possibility, CD34(+) and CD34(+)IL-5Ralpha(+) cells were measured in induced sputum from allergic subjects with asthma at baseline and at 7 and 24 hours after allergen and diluent inhalation, using flow cytometry. Isolated early responders (n = 9) were contrasted to dual responders (n = 9), who develop allergen-induced sputum and blood eosinophilia and airway hyperresponsiveness, and to normal control subjects. At baseline, there were significantly fewer sputum eosinophils and CD34(+) cells in normal control subjects compared with subjects with asthma. Sputum CD34(+) cells increased at 7 hours after allergen inhalation in both groups of subjects with asthma, which was sustained at 24 hours in the dual responder group only, associated with sustained increases in sputum CD34(+)IL-5Ralpha(+) cells, eosinophils, and interleukin-5. These results indicate that eosinophil progenitors can migrate to the airways and may differentiate toward an eosinophilic phenotype.

Kinetics of bone marrow eosinophilopoiesis and associated cytokines after allergen inhalation.

Allergen inhalation is associated with increased eosinophil/basophil progenitors in bone marrow 24 hours after allergen inhalation. This study examined the kinetics of eosinophilopoiesis in dual (n = 14), compared with isolated early, responders (n = 12). Dual responders, in contrast to isolated early responders, develop significant sputum and blood eosinophilia and prolonged airway hyperresponsiveness. Bone marrow aspirates were taken before and 5, 12, 24, and 48 hours after allergen inhalation. In dual responders, increases in interleukin (IL)-3-responsive progenitors were detected as early as 5 hours after allergen inhalation, and IL-5-responsive progenitors were detected at 12 and 24 hours. No changes were detected in isolated early responders. Bone marrow IL-5 protein levels increased at 12 and 24 hours in dual responders only and these increases correlated with increases in IL-5-responsive progenitors. In addition, bone marrow IFN-gamma levels increased in dual responders at 48 hours. These data demonstrate that, in dual responders, there is allergen-induced activation of an eosinophilopoietic process that is rapid and sustained, and a relationship between increased bone marrow IL-5 levels and increased eosinophil production. We propose that after allergen inhalation, time-dependent changes in cytokine levels in the bone marrow control differentiation of eosinophil/basophil progenitors.