Michael Manno

Baseline repeated measures from controlled human exposure studies: associations between ambient air pollution exposure and the systemic inflammatory biomarkers IL-6 and fibrinogen.

Introduction Systemic inflammation may be one of the mechanisms mediating the association between ambient air pollution and cardiovascular morbidity and mortality. Interleukin-6 (IL-6) and fibrinogen are biomarkers of systemic inflammation that are independent risk factors for cardiovascular disease. Objective We investigated the association between ambient air pollution and systemic inflammation using baseline measurements of IL-6 and fibrinogen from controlled human exposure studies. Methods In this retrospective analysis we used repeated-measures data in 45 nonsmoking subjects. Hourly and daily moving averages were calculated for ozone, nitrogen dioxide, sulfur dioxide, and particulate matter ≤ 2.5 μm in aerodynamic diameter (PM2.5). Linear mixed-model regression determined the effects of the pollutants on systemic IL-6 and fibrinogen. Effect modification by season was considered. Results We observed a positive association between IL-6 and O3 [0.31 SD per O3 interquartile range (IQR); 95% confidence interval (CI), 0.08–0.54] and between IL-6 and SO2 (0.25 SD per SO2 IQR; 95% CI, 0.06–0.43). We observed the strongest effects using 4-day moving averages. Responses to pollutants varied by season and tended to be higher in the summer, particularly for O3 and PM2.5. Fibrinogen was not associated with pollution. Conclusions This study demonstrates a significant association between ambient pollutant levels and baseline levels of systemic IL-6. These findings have potential implications for controlled human exposure studies. Future research should consider whether ambient pollution exposure before chamber exposure modifies IL-6 response.

Adherence to Multiple Sclerosis Disease-Modifying Therapies in Ontario is Low

BACKGROUND/OBJECTIVE Differences in patient adherence to various disease-modifying drugs (DMDs) in the treatment of multiple sclerosis (MS) are not well understood. The goal of this study was to evaluate adherence of adult MS patients in Ontario with public drug plan coverage to various DMDs: intramuscular interferon beta-1a (i.m. IFNβ-1a, Avonex), subcutaneous interferon beta-1a (s.c. IFNβ-1a, Rebif), subcutaneous interferon beta-1b (IFNβ-1b, Betaseron) or glatiramer acetate (Copaxone). METHODS In this retrospective cohort study, Ontario Public Drug Plan beneficiaries aged 15 or older who were newly treated with i.m. IFNβ-1a, s.c. IFNβ-1a, IFNβ-1b or glatiramer acetate between April 2006 and March 2008 were followed forward until treatment discontinuation, switch to another DMD or a maximum two year follow-up period. Cumulative persistence rates were analyzed by the Kaplan-Meier method. The proportion of patients reaching the study endpoints after the two year follow-up period was also calculated. RESULTS Cumulative persistence rates for all four DMDs were similar over time (p=0.80), ranging from 73.6-79.1% at six months, 59.1-63.1% at one year and 41.5-47.4% at two years. After two years, the proportion of patients who had discontinued treatment, switched to another DMD or died was similar among DMDs (p=0.79, Fishers exact test). Switching between DMD types was low and occurred in 3.4-6.5% of new DMD users. CONCLUSIONS Adherence to DMDs in adult MS patients in Ontario is poor, which is consistent with previously reported adherence rates to MS DMDs in other regions. No significant differences in adherence exist between the DMDs evaluated in this study.

Association Between Colonic Screening, Subject Characteristics, and Stage of Colorectal Cancer

OBJECTIVES:Colorectal cancer remains a significant cause of mortality and morbidity in North America. Colorectal cancer survival is highly dependent on stage at diagnosis, therefore it is important to identify factors related to stage. This study evaluated the association between subject factors (e.g., colonic screening, family history) and stage of colorectal cancer at diagnosis.METHODS:Population-based colorectal cancer cases recruited by the Ontario Familial Colon Cancer Registry between 1997 and 1999 were staged according to the tumor–nodal–metastasis (TNM) staging system and classified as early (TNM I/II) or late (TNM III/IV) stage. Epidemiologic information and stage was available for 768 cases. Multivariate logistic regression was used to obtain odds ratios (OR) estimates.RESULTS:Having had screening endoscopy reduced the risk of late stage diagnosis (OR = 0.46, 95% CI 0.22–0.98). Being older (>45 yr) was associated with a reduced risk of late stage cancer (OR = 0.36, 95% CI 0.18–0.74), as was having a first degree relative with colorectal cancer (OR =0.66, 95% CI 0.46–0.95). Rural residence (OR = 1.48, 95% CI 1.01–2.17) and non-white ethnicity (OR = 3.34, 95% CI 1.20–9.36) were associated with an increased risk of late stage cancer.CONCLUSIONS:Several factors are independently associated with late stage colorectal cancer. Colorectal cancer screening awareness and education programs need to consider targeting persons most likely to present with late stage colorectal cancer.

Describing the Burden of Upper-Extremity Musculoskeletal Disorders in Newspaper Workers: What Difference do Case Definitions Make?

Musculoskeletal disorders (MSD) of the upper limb are of growing concern, although there is no consensus on how to define a “case” of MSD. Varying the case definition has been shown to alter the description of the prevalence of the disorder. The purpose of this study was to compare the symptom description as well as the burden (disability costs, time off work) of MSD across four different published case definitions. A survey was conducted at a large urban newspaper, and 1003 (84% response rate) people responded. The questionnaire included measures of pain (intensity, frequency, duration), disability, work disability, and absence. Case definitions permitted creation of four overlapping samples, which were compared descriptively on the various measures of burden of MSD. The case definitions led to different descriptions of burden associated with MSD. Contrasting between the two extremes (Hunting and NIOSH), differences were found in prevalence (55% vs. 20%), overall disability (14.6 vs. 23.2/100, 100 = more disability) and difficulty at work (8 vs. 15.5/100), and proportion reporting pain interfering with work (27.3 vs. 16.2%). The various case definitions drew samples that were described by different experiences in terms of burden. Studies using different case definitions therefore lack comparability. The definition to use may depend on the study goals (primary or secondary prevention for example). However, consensus on a common definition would allow comparability across studies.

Use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and cardiovascular outcomes in chronic dialysis patients: a population-based cohort study.

Comment. To my knowledge this is the first study to report that smokers of mentholated cigarettes, and in particular women and non–African Americans, have significantly increased odds of stroke compared with nonmentholated cigarette smokers. Although potential causal links cannot be established and further research is required to confirm the findings, the association between mentholated cigarette smoking and stroke is noteworthy, given that the results are based on large population-level data, with data spanning nearly a decade, and given that the relationship is independent of multiple sociodemographic, smoking behavior, and health status confounders. The mentholated cigarette–stroke association may even be underestimated because this analysis included only current smokers and not former smokers. Increased cigarette particulate matter entering the lungs because of facilitation of reflex breath-holding through menthol-induced upper airway cold receptor stimulation serves as a potential mechanism for how mentholated cigarettes might potentially cause increased stroke over nonmentholated cigarettes. It is curious why smoking mentholated cigarettes would not result in an increase in forms of cardiovascular disease, other than stroke, like myocardial infarction and hypertension. A possible explanation is that mentholated cigarettes exert some selective effects on the cerebrovascular system. Potentially in support of this theory, smoking mentholated cigarettes has been found to result in increased carotid artery stiffness compared with smoking nonmentholated cigarettes, whereas equal decreases in coronary artery reserve flow were observed between the 2 cigarettes types. Other potential explanations for the mentholated cigarette–stroke relationship deserve mention. First, smokers with stroke may have a greater predisposition for smoking mentholated cigarettes than regular cigarettes (ie, reverse causality). Second, confounders not included in the analysis may potentially explain the association (eg, the presence or not of medical therapy). Third, the mentholated cigarette–stroke relationship may be erroneous, as a result of several sources of potential bias associated with the analysis (eg, recall bias, prevalence bias). Finally, there is less than 5% probability that the association found between mentholated cigarette smoking and stroke is one of chance. The fact that multiple disease outcomes were examined increases to some degree the finding of a “chance” association. These results highlight the need for further review of the last legally allowed tobacco additive in North America, given that mentholated cigarettes may be placing individuals at even greater risk of potentially devastating cerebrovascular disease than regular cigarettes.

Fluoroquinolone therapy and idiosyncratic acute liver injury: a population-based study

Background: Although fluoroquinolones are sometimes associated with mild, transient elevations in aminotransferase levels, serious acute liver injury is uncommon. Regulatory warnings have identified moxifloxacin as presenting a particular risk of hepatotoxicity. Thus, we examined the risk of idiosyncratic acute liver injury associated with the use of moxifloxacin relative to other selected antibiotic agents. Methods: We conducted a population-based, nested, case–control study using health care data from Ontario for the period April 2002 to March 2011. We identified cases as outpatients aged 66 years or older with no history of liver disease, and who were admitted to hospital for acute liver injury within 30 days of receiving a prescription for 1 of 5 broad-spectrum antibiotic agents: moxifloxacin, levofloxacin, ciprofloxacin, cefuroxime axetil or clarithromycin. For each case, we selected up to 10 age- and sex-matched controls from among patients who had received a study antibiotic, but who were not admitted to hospital for acute liver injury. We calculated odds ratios (ORs) to determine the association between admission to hospital and previous exposure to an antibiotic agent, using clarithromycin as the reference. Results: A total of 144 patients were admitted to hospital for acute liver injury within 30 days of receiving a prescription for one of the identified drugs. Of these patients, 88 (61.1%) died while in hospital. After multivariable adjustment, use of either moxifloxacin (adjusted OR 2.20, 95% confidence interval [CI] 1.21–3.98) or levofloxacin (adjusted OR 1.85, 95% CI 1.01–3.39) was associated with an increase in risk of acute liver injury relative to the use of clarithromycin. We saw no such risk associated with the use of either ciprofloxacin or cefuroxime axetil. Interpretation: Among older outpatients with no evidence of liver disease, moxifloxacin and levofloxacin were associated with an increased risk of acute liver injury relative to clarithromycin.

Concentrated ambient fine particles and not ozone induce a systemic interleukin-6 response in humans.

Epidemiological studies have established significant associations between ambient pollutants, including fine particulate matter (PM2.5) and ozone (O3), and cardiopulmonary morbidity and mortality. One mechanism that has been proposed is a pulmonary/systemic inflammatory response. Although controlled human exposure studies have examined the independent inflammatory responses of PM2.5 and O3, no studies have previously examined their joint effects. The study objective was to examine the independent and combined associations between ambient PM2.5 and O3 and acute respiratory/inflammatory responses. Using their concentrated ambient particle (CAP) facility for PM2.5, the authors studied 10 mild asthmatic and 13 nonasthmatic individuals. The 2-h exposures included CAP (range 48–199 μg/m3) and filtered air (FA), with/without O3 (120 ppb), in a randomized block design. Response measures included pulmonary function and inflammatory indices in induced sputum (interleukin [IL]-6, cytology) and blood (IL-6, tumor necrosis factor [TNF]-α) measured before and after exposures. Three hours post exposure, there was an increase in blood levels of IL-6, but only after CAP alone exposures; the IL-6 increase was associated with increasing PM2.5 mass concentration (p = .005). Some individuals switched to shallow breathing during CAP+O3, possibly accounting for an attenuation of the resultant blood IL-6 response. Asthmatic and nonasthmatic responses were similar. There were no adverse changes in pulmonary function or other inflammatory measures. The study demonstrated an acute IL-6 response to PM2.5, providing evidence to support the epidemiological findings of associations between ambient levels of particles and cardiopulmonary morbidity and mortality.

Reduction in diisocyanate and non-diisocyanate sensitizer-induced occupational asthma in Ontario.

Objective: To investigate relative frequency and features of diisocyanate (ISO) and non-diisocyanate (N-ISO) allowed occupational asthma (OA) claims in Ontario, Canada, during a 5-year period (1998 to 2002). Methods: Records were abstracted from the Ontario Workplace Safety and Insurance Board using methodology similar to our previous investigation that had identified 30 ISO and 30 N-ISO claims/yr during 1980 to 1993. Results: There were 99 OA claims: 37 ISO (7.4 claims/yr) and 62 N-ISO (12.4 claims/yr). The ISO group had more males (86% vs 69%, p = 0.01), but there were no other significant differences. The commonest professions were spray painters (41%) and production workers (38%) in the ISO group and production workers (49%) and health care workers (8%) in the N-ISO group. Conclusions: ISO and N-ISO claims declined from the previous period, especially for ISO, perhaps because of effective surveillance programs.

Upper extremity disability in workers with hand–arm vibration syndrome

BACKGROUND Hand-arm vibration syndrome (HAVS) is a common occupational problem and it is important to understand the disability associated with this condition. AIMS To measure upper extremity disability using the disabilities of the arm, shoulder and hand (DASH) questionnaire in workers with HAVS and to determine how this disability is affected by the vascular and neurological components of HAVS and other factors, in particular musculoskeletal variables. METHODS Subjects were recruited from HAVS patients assessed at St Michaels Hospital, Toronto, Canada, over a 2-year period. All participants were assessed by an occupational medicine specialist to determine the specific components of HAVS and musculoskeletal variables including upper extremity pain score measured by the Borg scale. The DASH questionnaire was completed on the same day as the clinical assessment and before any feedback had been given about the clinical findings. RESULTS A total of 141 workers with HAVS were recruited and 139 agreed to participate in the study. This study group had a statistically significantly higher mean DASH score than the US population (P < 0.001). The multiple linear regression analysis indicated that upper extremity pain score (P < 0.001), the Stockholm sensorineural scale (P < 0.01) and the number of fingers blanching (P < 0.05) had a statistically significant association with an increase in the DASH score. The highest partial R(2) value was for the upper extremity pain score. CONCLUSIONS Workers with HAVS have significant upper extremity disability and musculoskeletal factors appear to make an important contribution to this disability.

Symptoms after mould exposure including Stachybotrys chartarum, and comparison with darkroom disease

To cite this article: Al‐Ahmad M, Manno M, Ng V, Ribeiro M, Liss GM, Tarlo SM. Symptoms after mould exposure including Stachybotrys chartarum, and comparison with darkroom disease. Allergy 2010; 65: 245–255.