Publications

OBJECTIVE

To assess the annual lung function decline associated with the reduction of secondhand smoke exposure in a high-altitude industrial workforce.

METHODS

We performed pulmonary function tests annually among 109 high-altitude gold-mine workers over 5 years of follow-up. The first 3 years included greater likelihood of exposure to secondhand smoke exposure before the initiation of extensive smoking restrictions that came into force in the last 2 years of observation.

RESULTS

In repeated measures modeling, taking into account the time elapsed in relation to the smoking ban, there was a 115 ± 9 (standard error) mL per annum decline in lung function before the ban, but a 178 ± 20 (standard error) mL per annum increase afterward (P < 0.001, both slopes).

CONCLUSION

Institution of a workplace smoking ban at high altitude may be beneficial in terms of lung function decline.

BACKGROUND

Lung transplant (LT) aims to extend survival and improve patient-centred outcomes (PCOs) by reducing disability and improving health-related quality of life (HRQL). Few PCO instruments have been validated in LT populations. We aimed to develop and validate a shortened version of the valued life activities (VLA) disability scale specific to LT.

METHODS

We used data from 140 subjects participating in an ongoing cohort study of LT. Subjects completed a survey battery, including VLA items, and physical assessments before LT. To develop a shortened LT-specific VLA (LT-VLA), we iteratively deleted items from a longer 32-item VLA battery, retaining the instrument's conceptual framework, scoring and performance characteristics. We evaluated LT-VLA validity by testing correlations with a HRQL measure (Short Form-12 Physical Function (SF-12 PF) subscale), forced vital capacity % (FVC%) predicted and 6 minute walk distance (6MWD). Responsiveness was evaluated in 84 subjects who completed assessments before and after LT.

RESULTS

The 15-item LT-VLA scoring closely matched the longer VLA (correlations ≥0.96) and had excellent internal consistency (Cronbach's α 0.92). The LT-VLA required only 3 min or less to administer. The LT-VLA, measured as mean difficulty in performing each of the 15 activities queried, correlated with FVC% predicted (r=-0.30), 6MWD (r=-0.38) and SF-12 PF (r=-0.47) (all p<0.01). The LT-VLA mean difficulty was responsive to change from before to after LT (63% improvement; effect size=1.60).

CONCLUSIONS

The LT-VLA is a short, easy to administer, valid and responsive disease-specific PCO instrument that may be useful in clinical and research applications for lung transplantation.

BACKGROUND

While exposure to outdoor particulate matter (PM) has been associated with poor asthma outcomes, few studies have investigated the combined effects of outdoor and indoor PM (including secondhand tobacco smoke).

OBJECTIVE

To examine the associations between PM and asthma outcomes.

METHODS

We analyzed data from a cohort of adults with asthma and rhinitis (n=302; 82% both conditions; 13% asthma only; 5% rhinitis alone) including measures of home PM, tobacco smoke exposure (hair nicotine and self-report), ambient PM from regional monitoring, distance to roadway, and season (wet or dry). The outcomes of interest were frequent respiratory symptoms and forced expiratory volume in 1 second (FEV1) below the lower limit of normal (NHANES reference values). Multivariable regression analyses examined the associations (Odds Ratio [OR] and 95% Confidence Interval [95%CI]) between exposures and these outcomes, adjusted by sociodemographic characteristics.

RESULTS

In adjusted analyses of each exposure, the highest tertile of home PM and season of interview were associated with increased odds for more frequent respiratory symptoms (OR=1.64 95%CI: [1.00, 2.69] and OR=1.66 95%CI: [1.09, 2.51]). The highest tertile of hair nicotine was significantly associated with FEV1 below the lower limit of normal (OR=1.80 95%CI: [1.00, 3.25]). In a model including home PM, ambient PM, hair nicotine, and season, only two associations remained strong: hair nicotine with FEV1 below the lower limit of normal and season of measurement (dry, April-October) with increased respiratory symptoms (OR=1.85 95%CI: [1.00, 3.41] and OR=1.54 95%CI: [1.0, 2.37]). When that model was stratified by sex, the highest tertiles of ambient PM and hair nicotine were associated with FEV1 below the lower limit of normal among women (OR=2.23 95%CI: [1.08, 4.61] and OR=2.90 95%CI: [1.32, 6.38]), but not men. The highest tertile of hair nicotine was also associated with increased respiratory symptoms in women but not men (OR=2.38 95%CI: [1.26, 4.49]). When stratified by age, the middle quartile of ambient PM and the highest hair nicotine tertile were associated with increased respiratory symptoms (OR=2.07 95%CI: [1.01, 4.24] and OR=2.55 95%CI: [1.21, 5.36]) in those under 55 but not in the older stratum.

CONCLUSIONS

Exposure to PM from both home and ambient sources is associated with increased symptoms and lower lung function in adults with asthma, although these associations vary by type of PM, the respiratory outcome studied, sex and age.

RATIONALE

HIV seropositivity has long been considered a contraindication to lung transplantation, primarily because of the potential risks of added immunosuppression. In the past decade, however, experience with kidney and liver transplantation in the setting of HIV infection, with achievement of satisfactory outcomes, has grown considerably. This promising development has created a need to reconsider this contraindication to lung transplantation.

OBJECTIVES

There is presently limited evidence upon which to base medical decision-making regarding lung transplantation in individuals with HIV infection. In our present study, we wished to extend the existing literature by reporting the outcomes of three individuals with HIV infection who underwent lung transplantation at two centers.

METHODS

We compiled data for a case series of three HIV-infected subjects undergoing lung transplantation at two centers.

MEASUREMENTS AND MAIN RESULTS

We reviewed medical records to investigate the effects of lung transplantation on the course of HIV infection, the development of HIV-related opportunistic infections or malignancies, the occurrence of lung transplant and HIV drug interactions, and the extent of acute rejection. Subject 1, who underwent transplantation for HIV-associated pulmonary arterial hypertension, experienced recalcitrant acute rejection requiring a lymphocyte-depleting agent with subsequent rapid development of bronchiolitis obliterans syndrome. Subjects 2 and 3, who underwent transplantation for idiopathic pulmonary fibrosis, experienced mild acute rejection but remain free from chronic rejection at 4 and 2 years after transplant, respectively.

CONCLUSIONS

Lung transplantation may be feasible for carefully selected patients in the setting of controlled HIV infection. On the basis of our experience with three patients, we caution that acute graft rejection may be more common in such patients.

BACKGROUND

Studies of occupational acute mountain sickness (AMS) have not focused on the more severe end of the spectrum to date.

AIMS

To examine risk factors associated with the development of occupational AMS severe enough to receive treatment in a compression chamber.

METHODS

A nested case referent study in a cohort of high-altitude (4000 m) mine workers, comparing cases of severe, chamber-treated AMS to matched referents. Using logistic regression, we tested potential risk factors based on premorbid surveillance examinations, including cigarette smoking (current smoking, smoking intensity and exhaled carbon monoxide [CO]).

RESULTS

There were 15 cases and 30 controls. In multivariate analysis including age, sex and place of residence, current smoking was associated with increased risk of severe AMS (odds ratio [OR] 10.0; 95% confidence interval [CI] 1.5-67.4), taking into account any prior, less severe AMS event, which was also a potent risk factor (OR 33.3; 95% CI 2.8-390). Smoking intensity (cigarettes per day) and exhaled CO were also statistically significantly associated with severe AMS.

CONCLUSIONS

Cigarette smoking is a strong, previously under-appreciated risk factor for severe AMS. Because this is a modifiable factor, these findings suggest that workplace-based smoking cessation should be tested as an intervention to prevent such morbidity.

OBJECTIVE

We sought to quantify absorption of triclosan, a potential endocrine disruptor, in health care workers with occupational exposure to soap containing this chemical.

METHODS

A cross-sectional convenience sample of two groups of 38 health care workers at separate inpatient medical centers: hospital 1 uses 0.3% triclosan soap in all patient care areas; hospital 2 does not use triclosan-containing products. Additional exposure to triclosan-containing personal care products was assessed through a structured questionnaire. Urine triclosan was quantified and the occupational contribution estimated through regression modeling.

RESULTS

Occupational exposure accounted for an incremental triclosan burden of 206 ng/mL (P = 0.02), while triclosan-containing toothpaste use was associated with 146 ng/mL higher levels (P < 0.001).

CONCLUSIONS

Use of triclosan-containing antibacterial soaps in health care settings represents a substantial and potentially biologically relevant source of occupational triclosan exposure.

BACKGROUND

Manual cigarette lighter refilling with butane/propane admixed liquefied petroleum gas (LPG) is a common low-income occupation in India. This practice may cause adverse health effects from LPG exposure among such workers.

OBJECTIVE

To assess respiratory status among LPG-exposed workers and non-exposed controls.

METHODS

We quantified the exposure and evaluated respiratory symptoms and lung function among 113 LPG refilling workers (aged 41.9±9.9 years) and 79 controls (aged 40.8±7.2 years). We used multiple linear regression analysis to estimate the LPG exposure response within the group of refilling workers, adjusting for age, height and smoking status.

RESULTS

Compared to the controls, the LPG-exposed lighter refillers manifested a 190 ml decrement in 1-second forced expiratory volume (FEV1) (2.55±0.4 vs. 2.26±0.3 l) and a 6% decrement in FEV1/forced vital capacity (FVC) (both P < 0.05). We found a significantly negative exposure response among the LPG workers: for FVC and FEV1, 44 ml per ml of reported daily LPG use in refilling (P < 0.05).

CONCLUSION

Likely heavy exposure to LPG through manually refilling cigarette lighters is associated with airflow decrements. This adverse effect may be relevant to other occupational groups heavily exposed to volatile hydrocarbons, especially those in marginal employment sectors.

BACKGROUND

Attacks of neuropathic pain, usually abdominal, are characteristic of the acute porphyrias and accompanied by overproduction of heme-precursor molecules, specifically delta-aminolevulinic acid and porphobilinogen. The basis for the acute symptoms in these diseases has been speculative.

METHODS

We review genetic acute porphyria, hereditary tyrosinemia, and an acquired condition, lead poisoning. All perturb heme synthesis and present with a similar pain syndrome.

RESULTS

Although each of these conditions has characteristic urine biochemistry, all exhibit excess delta-aminolevulinic acid. Moreover, in all, treatment with hemin reduces delta-aminolevulinic acid and relieves symptoms. In contrast, use of recombinant porphobilinogen deaminase to knock down porphobilinogen in acute porphyria was ineffective.

CONCLUSIONS

There is now convincing evidence that delta-aminolevulinic acid is the cause of pain in the acute porphyrias. The efficacy of hemin infusion is due mainly, if not entirely, to its inhibition of hepatic delta-aminolevulinic acid synthase-1, the enzyme that catalyzes delta-aminolevulinic acid formation. Delta-aminolevulinic acid synthase-1 is a rational target for additional therapies to control symptoms in acute porphyria.

PURPOSE

Health-related quality of life (HRQL) domains vary across disease conditions and are determined by standards, values, and priorities internal to patients. Although the clinical goals of lung transplantation are to improve patient survival and HRQL, what defines HRQL in lung transplantation is unknown. Employing a qualitative approach, we aimed to identify HRQL domains important in lung transplantation.

METHODS

We conducted semi-structured interviews in purposefully sampled lung transplant recipients (n = 8) representing a spectrum of ages, gender, indications for transplantation, and time since transplantation as well as healthcare practitioners representing a spectrum of practitioner types (n = 9). Grounded theory was used to identify HRQL domains important in lung transplantation, building on but going beyond domains already defined in the SF-36, the most commonly used instrument in this population.

RESULTS

In addition to confirming the relevance of the eight SF-36 domains, we identified 11 novel HRQL domains. Palliation of respiratory symptoms was identified as important. After transplant surgery, new HRQL domains emerged including: distressing symptoms spanning multiple organ systems, worry about infection and acute rejection, treatment burden, and depression. Further, patients identified challenges to intimacy, changes in social relationships, and problems with cognitive functioning. Saliently, worry about limited life expectancy was pervasive and impaired life planning.

CONCLUSIONS

We found that HRQL in lung transplantation is defined by both generic and transplant-specific domains. Delineating and refining these domains can inform efforts to improve clinical outcomes and HRQL measurement in lung transplantation.

PURPOSE

Chronic obstructive pulmonary disease (COPD) is associated with substantial morbidity, including impaired health-related quality of life (HRQoL). Despite the prominent role of occupational factors in the aetiology of COPD, the relationship between these exposures and HRQoL has not been well elucidated.

METHODS

A subpopulation from an epidemiological study, designed to assess the workplace contribution to COPD, was administered the EQ5D HRQoL tool. Demographics, an index of economic deprivation, health endpoints including the presence of COPD and lung function were also recorded. Workplace exposures were categorised using both self-reported exposures and also by the use of an established job exposure matrix (JEM).

RESULTS

A total of 623 individuals participated (mean age 67.1 years). One hundred and forty-eight (24%) reported having received a physician diagnosis of COPD, 355 (57%) were male, and 386 (62%) were ever smokers. As anticipated, the presence of COPD was associated with a poorer HRQoL. Additionally, however, HRQoL was significantly lower in the presence of both self-reported vapours, gases, dusts and fumes exposure and JEM-based exposure irrespective of the presence of COPD. Regression analysis, adjusting for a variety of covariates including the presence of COPD, confirmed a persisting higher likelihood of occupational exposure categorised by JEM being associated with poorer HRQoL scores (β estimate: -0.069; p < 0.05).

CONCLUSIONS

Our findings suggest that work may have an important link to HRQoL and that this effect can persist even among those who have retired. In those with COPD, HRQoL is worse than among those without this condition, but the work-associated decrement appears to be similar across both groups.