RESUMEN
RATIONALE: Acute asthma exacerbations, precipitated by viral infections, are a significant cause of morbidity, but not all patients with asthma are equally susceptible. OBJECTIVES: To explore susceptibility factors for asthma exacerbations, we considered a role for histoblood group antigens because they are implicated in mechanisms of gastrointestinal viral infection, specifically the O-secretor mucin glycan phenotype. We investigated if this phenotype is associated with susceptibility to asthma exacerbation. METHODS: We performed two consecutive case-control studies in subjects with asthma who were either prone or resistant to asthma exacerbations. Exacerbation-prone cases had frequent use of prednisone for an asthma exacerbation and frequent asthma-related healthcare utilization, whereas exacerbation-resistant control subjects had rarely reported asthma exacerbations. The frequency of different mucin glycan phenotypes, defined by the presence or absence of H (O), A, B, or AB antigens, was compared in cases and control subjects. MEASUREMENTS AND MAIN RESULTS: In an initial study consisting of 49 subjects with asthma (23 cases and 26 control subjects), we found that having the O-secretor phenotype was associated with a 5.8-fold increase in the odds of being a case (95% confidence interval, 1.7-21.0; P = 0.006). In a replication study consisting of 204 subjects with asthma (101 cases and 103 control subjects), we found that having the O-secretor phenotype was associated with a 2.3-fold increased odds of being a case (95% confidence interval, 1.2-4.4; P = 0.02). CONCLUSIONS: The O-secretor mucin glycan phenotype is associated with susceptibility to asthma exacerbation. Clinical trial registered at www.clinicaltrials.gov (NCT00201266).
Asunto(s)
Antígenos Bacterianos/sangre , Asma/inmunología , Susceptibilidad a Enfermedades/inmunología , Mucosa Respiratoria/inmunología , Adolescente , Adulto , Anciano , Asma/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Susceptibilidad a Enfermedades/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Mucosa Respiratoria/metabolismo , Factores de Riesgo , Saliva/metabolismo , Adulto JovenRESUMEN
Although automotive friction products (brakes and manual clutches) historically contained chrysotile asbestos, industrial hygiene surveys and epidemiologic studies of auto mechanics have consistently shown that these workers are not at an increased risk of developing asbestos-related diseases. Airborne asbestos levels during brake repair and brake parts handling have been well-characterized, but the potential exposure to airborne asbestos fibers during the handling of clutch parts has not been examined. In this study, breathing zone samples on the lapel of a volunteer worker (n=100) and area samples at bystander (n=50), remote area (n=25), and ambient (n=9) locations collected during the stacking, unpacking, and repacking of boxes of asbestos-containing clutches, and the subsequent cleanup and clothes handling, were analyzed by phase contrast microscopy (PCM) and transmission electron microscopy (TEM). In addition, fiber morphology and size distribution was evaluated using X-ray diffraction, polarized light microscopy, and ISO analytical methods. It was observed that the (1) airborne asbestos concentrations increased with the number of boxes unpacked and repacked, (2) repetitive stacking of unopened boxes of clutches resulted in higher asbestos concentrations than unpacking and repacking the boxes of clutches, (3) cleanup and clothes handling tasks yielded very low asbestos concentrations. Fiber size and morphology analyses showed that amphibole fibers were not detected in the clutches and that the vast majority (>95%) of the airborne chrysotile fibers were less than 20 microm in length. Applying the ratio of asbestos fibers:total fibers (including non-asbestos) as determined by TEM to the PCM results, it was found that 30-min average airborne chrysotile concentrations (PCM adjusted) were 0.026+/-0.004 f/cc or 0.100+/-0.017 f/cc for a worker unpacking and repacking 1 or 2 boxes of clutches, respectively. The 30-min PCM adjusted average airborne asbestos concentrations at bystander locations ranged from 0.002+/-0.001 f/cc and 0.004+/-0.002 f/cc when 1 or 2 boxes of clutches were handled, respectively. Estimated 8-h TWA asbestos exposures for a worker handling 1 or 2 boxes of clutches over a workday ranged from 0.002 to 0.006 f/cc. The 30-min PCM adjusted average airborne asbestos concentration for a worker continuously stacking unopened boxes of clutches was 0.212+/-0.014 f/cc; the 8-h TWA was 0.013 f/cc. Additionally, 30-min PCM adjusted average airborne asbestos concentrations following cleanup and clothing handling were 0.002+/-0.001 f/cc and 0.002+/-0.002 f/cc, respectively, both resulting in estimated 8-h TWA asbestos exposures of 0.0001 f/cc. The results of this study indicate that the handling, unpacking, and repacking of clutches, and the subsequent cleanup and clothes handling by a worker within a short-term period or over the entire workday, result in exposures below the historical and current short-term and 8-h occupational exposure limits for asbestos.