Association Between Urinary Phthalate Metabolites and Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study.

Objective: To determine the association of urinary phthalate metabolites with chronic obstructive pulmonary disease (COPD), airflow obstruction, lung function and respiratory symptoms. Methods: Our study included a total of 2023 individuals aged ≥ 40 years old in the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression was conducted to explore the correlation of eleven urinary phthalate metabolites (MCNP, MCOP, MECPP, MnBP, MCPP, MEP, MEHHP, MEHP, MiBP, MEOHP, and MBzP) with COPD, airflow obstruction and respiratory symptoms. Linear regression analyses were used to evaluate the relationship between urinary phthalate metabolites and lung function. Results: When compared to the first tertile, the third tertile of MEHHP was associated with the risk of COPD [OR: 2.779; 95% confidence interval (CI): 1.129-6.840; P = 0.026]. Stratified analysis showed that MEHHP increased the risk of COPD by 7.080 times in male participants. Both MCPP and MBzP were positively correlated with the risk of airflow obstruction. The third tertile of MBzP increased the risk of cough by 1.545 (95% CI: 1.030-2.317; P = 0.035) times. Both FEV1 and FVC were negatively associated with MEHHP, MECPP, MnBP, MEP, MiBP and MEOHP. Conclusion: Higher levels of MEHHP are associated with increased risk of COPD, and lower measures of FEV1 and FVC. MBzP is positively related to airflow obstruction and cough.

Exposure of health care workers to aerosolized pentamidine.

In patients, urinary levels of pentamidine have been shown to reflect pulmonary deposition of aerosolized drug. Using urinary levels and air filter samples, we assessed factors responsible for health care worker (HCW) exposure. We measured serial urine samples in HCWs who administered aerosol pentamidine over an 11-month period and compared them with serial urine levels measured over 30 days in a normal volunteer in whose lungs a known amount of pentamidine (3.39 mg) had been deposited. Ambient exposure to pentamidine was determined by continuous high volume air sampling in the treatment room during routine therapy. In addition, the amount of pentamidine released by six HIV-positive subjects, performing tidal breathing with a Respirgard II nebulizer in an airtight booth, was measured by extracting air from the booth through a filter. The effect of adding noseclips, of coughing (with nebulizer shut down), and of removing the nebulizer from the patient's mouth without turning it off, were determined. Pentamidine in the urine of the normal volunteer reached a peak concentration of 9.5 ng/mg creatinine/ml and was detectable for 30 days following the exposure. In HCWs, pentamidine was detected intermittently in four of five individuals with levels as high as 18.2 ng/mg creatinine/ml. Samples of ambient treatment room air indicated small daily releases of pentamidine (0.013 +/- 0.02 mg per patient treated), but simultaneous urine levels in HCWs were negative. The data from the airtight booth revealed that removing the nebulizer from a patient's mouth without turning it off caused a 360-fold increased in pentamidine release compared to tidal breathing. Coughing resulted in a 6.9 (range 0.9-14.2)-fold increase in release, while the addition of noseclips had no significant effect. The pattern of intermittently positive urine tests and the low levels of ambient pentamidine detected in the air of the treatment room suggest that HCWs are being exposed to episodic but high concentrations of pentamidine. High level exposure is most likely to occur during treatment interruptions which are usually precipitated by coughing episodes. Because of the intermittent pattern of exposure and slow clearance of pentamidine, urine assay is useful for detecting high intermittent exposure. Random air sampling is a sensitive indicator of low level exposures but may not detect episodic high level releases.

Prospective longitudinal study of urinary eosinophil protein X in children with asthma and chronic cough.

Airway inflammation is the principal abnormality in asthma and many other respiratory diseases. Eosinophils are the cells primarily involved in this process. The aim of this study was to analyze sequential changes in urinary eosinophil protein X (EPX) a biological marker of eosinophil activation in asthmatic children and chronic coughers, and to confirm the importance of such changes in evaluating the inflammatory process once regular treatment was initiated. Eighty-eight asthmatic children (AC), 33 children with chronic cough (CC), and 34 control children were included in the study. All those with respiratory disease underwent allergy tests (serum total IgE, serum-specific IgE for common allergens, peripheral blood eosinophil (PBE), and skin prick tests) and a pulmonary function test (PFT), and had chest X-ray and serum eosinophil cationic protein (s-ECP) and urinary EPX assays. All subjects attended the outpatient clinic every 3 months, irrespective of the treatment prescribed following inclusion in this investigation. At baseline, urinary EPX concentrations were higher in children with asthma and those with chronic cough than in controls (mean 171.1 and 131.3, respectively, vs. 60.2 microg/mmol creatinine, P < 0.001). CC children had lower eosinophil counts (0.25 vs. 0.39 x 10(9)/L, P < 0.02) than those with asthma. There was no significant difference between the AC and CC groups in urinary EPX and s-ECP levels. s-ECP concentrations were significantly higher (P < 0.01) in atopic vs. nonatopic patients (44 vs. 29.9 ng/mL), but no significant difference was observed for urinary EPX. Concentrations of urinary EPX were significantly correlated with s-ECP levels (r = 0.24, P < 0.025) and with PBE (r = 0.38, P < 0.01). No correlation was found between urinary EPX values and PFT results. In AC receiving inhaled steroids after the start of the study, there was a significant reduction after 3 months in urinary EPX (-54, P < 0.02). In contrast, there was no significant change in PBE levels. Urinary EPX concentrations are sensitive, noninvasive technique that could be useful to the clinician in the evaluation of manifestations of airway inflammation.