Effect of supplementation with beta-carotene and vitamin A on lung nutrient levels.

The Carotene and Retinol Efficacy Trial (CARET), a randomized, placebo-controlled lung cancer chemoprevention trial of 30 mg of beta-carotene and 25,000 IU of retinyl palmitate, was prematurely terminated when a 46% excess lung cancer mortality was found in subjects on the active arm. Before the CARET intervention ended, 21 men were recruited to participate in a 6-month biomarker study using the same intervention as CARET that determined the effect of this supplementation on lung nutrient levels. Plasma and bronchoalveolar lavage (BAL) cell nutrient levels were measured before and after the intervention. The group in the active arm (n = 10) had plasma carotene level increases of over 10-fold, with a small increase in plasma retinol levels BAL cell levels of beta-carotene in the active group also increased 10-fold, from 4.5 to 46.3 pmol/10(6) cells (P = 0.0008), with no change in BAL cell retinol levels. Surgically obtained lung tissue from three CARET subjects in the active arm showed elevated carotene lung tissue levels but no increase in lung retinol levels compared to a group of surgical controls. Combined with our previous work showing a strong correlation between BAL and lung tissue nutrient levels, these findings suggest that supplementation with beta-carotene and vitamin A results in increased lung tissue as well as BAL cell levels of beta-carotene, with little change in lung retinol.

Airway isocyanate-adducts in asthma induced by exposure to hexamethylene diisocyanate.

OBJECTIVES: The clinical features, airway histology, and detection of hexamethylene diisocyanate (HDI) protein adducts in endobronchial biopsies from a patient with HDI asthma are described. METHODS: Isocyanate asthma was diagnosed by history, methacholine challenge, and workplace HDI challenge. Bronchoscopy was performed 24 h after challenge and immunohistochemical staining was performed. RESULTS: Airway biopsies obtained at bronchoscopy demonstrated inflammatory changes typical for asthma, including increased airway eosinophils and T cells. Immunohistochemical staining with specific anti-HDI antibodies demonstrated the presence and localization of HDI adducts in human bronchial biopsies. CONCLUSIONS: These studies confirm epithelial exposure to HDI following workplace challenge and demonstrate the feasibility of detecting and localizing isocyanate adducts in human lung tissue. Identifying and characterizing the airway macromolecules to which isocyanates bind in vivo are probably crucial to the understanding of how isocyanates cause sensitization and asthma. The ability to detect isocyanate adducts may also help characterize isocyanate exposure patterns and exposure-disease relationships.

Human gamma/delta T-cell lines derived from airway biopsies.

gamma/delta T cells have been postulated to play an important role in the immune response at epithelial boundaries, but have not been well described in human lung tissue. We have identified and characterized gamma/delta T-cell lines from human airway biopsies and compared them with T-cell lines from paired peripheral blood samples. Airway-derived T-cell lines stimulated with tetanus toxoid (TT) contained a greater proportion of gamma/delta T cells compared with T-cell lines stimulated with mitogens, other antigens, or without antigen. TT-stimulated airway T cells expressed different T-cell receptors (TCRs) than did blood- derived T cells, and used predominantly variable region (V)gamma I family genes rather than V gamma II family genes. Airway-derived gamma/delta T cells produced high levels of interferon-gamma and were associated with T helper 1--like cytokine profiles. This study describes the presence and antigen-dependent proliferation of gamma/delta T cells from human airway tissue, and demonstrates differences in lung-derived gamma/delta TCRs compared with gamma/delta T cells derived from peripheral blood. The data suggest that gamma/delta T cells may be functionally enriched in human airways relative to peripheral blood.

Diisocyanate-exposed auto body shop workers: a one-year follow-up.

BACKGROUND: Diisocyanates currently are the most commonly identified cause of occupational asthma in industrialized countries. Auto body shops, a common hexamethylene diisocyanate (HDI) exposure setting, are difficult to study due to their small size and episodic exposures. OBJECTIVES: A 1-year follow-up was undertaken as an adjunct to the cross-sectional SPRAY study (Survey of Painters & Repairers of Auto bodies by Yale) to investigate the effects of HDI on auto body shop workers over time and whether or not the healthy worker effect may exist in this industry. METHODS AND RESULTS: Forty-eight workers from seven shops were re-contacted. Thirty-four subjects who stayed at the same shop and 11 who left their original shop participated. No statistically significant changes in physiology, symptoms, and immunologic responses from baseline to follow-up were noted. However, significant differences between those who left the shops and those who stayed were noted. Those who left were younger, less experienced in the industry, and more likely to have a history of asthma (23 vs. 3%; P < 0.05), bronchial hyper-responsiveness (23 vs. 9%), HDI-specific IgG (64 vs. 29%; P < 0.05), and HDI-specific proliferation (S.I. 2.0 vs. 1.3; P < 0.05). CONCLUSIONS: The differences in workers who stayed at their shop compared to those who left, combined with the low asthma prevalence and high job turnover rate, all suggest that a healthy worker effect may exist in the auto body industry, and may in part account for the low prevalence of asthma noted in SPRAY and other cross-sectional studies of diisocyante workers.

Qualitative assessment of isocyanate skin exposure in auto body shops: a pilot study.

BACKGROUND: Little is known about the extent of human isocyanate skin exposure in auto body shops and the effectiveness of personal protective equipment. Animal studies have suggested that skin exposure to isocyanates may be an important risk factor for respiratory sensitization leading to asthma. This study provides initial data on hexamethylene diisocyanate skin exposure in three auto body shops. METHODS: Three auto body shops of different size which use different paint systems were examined for the presence of aliphatic isocyanates on environmental surfaces and workers' skin and for breakthrough of personal protective equipment. Qualitative detection of contamination by isocyanates was conducted using a wipe-sampling technique. Assessment focused on the painters and their tasks, although other auto body repairers were also evaluated. RESULTS: Environmental surfaces such as painters' workbenches, spray equipment, and cleaning tools were found contaminated with isocyanates. Painters had frequent contact with contaminated surfaces, often without wearing gloves. Moderate to heavy contamination of some skin surfaces was found with painters from two of the three auto body shops. Latex gloves used for skin protection showed significant penetrations by isocyanates even after a single painting session. CONCLUSIONS: Contaminated environmental surfaces and skin exposure to isocyanates were documented in several auto body shops. Latex gloves were not adequate protection for workers using isocyanate paints. Further research which would better quantify skin exposure, and its potential relationship to respiratory sensitization and asthma is warranted.

Subclinical immunologic and physiologic responses in hexamethylene diisocyanate-exposed auto body shop workers.

BACKGROUND: Diisocyanates are potent sensitizing agents and currently the most commonly identified cause of occupational asthma in industrialized countries. However, diisocyanate asthma is difficult to diagnose and exposure and host risk factors are unclear. Auto body shops, one of the most common hexamethylene diisocyanate (HDI) exposure settings, are particularly difficult to study due to their small size and episodic exposures. Surveillance studies of such workers are limited. OBJECTIVES: We have initiated a cross-sectional field epidemiologic study, Survey of Painters and Repairers of Auto bodies by Yale (SPRAY), to characterize the effects of diisocyanate exposures on actively employed auto body shop workers. Methods and Results We present here questionnaire, physiologic, immunologic, and exposure data on 75 subjects enrolled in the study. No overt cases of clinically apparent diisocyanate asthma were identified based on spirometry, methacholine challenge, peak flows, and symptoms. HDI-specific lymphocyte proliferation was present in 30% of HDI-exposed workers and HDI-specific IgG in 34% of HDI-exposed workers, but they were not associated. HDI-specific IgE was detected in two workers. HDI-specific lymphocyte proliferation, increased methacholine responsiveness, and symptoms of chest tightness and shortness of breath were more common in the most heavily HDI-exposed workers, the painters. More long-term follow-up of this cohort should clarify the significance of these HDI-specific immunologic responses, physiologic changes, and symptoms. CONCLUSIONS: These findings demonstrate the presence of HDI-specific immune responses in a large proportion of healthy HDI-exposed workers.